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Dietary açai attenuates hepatic steatosis via adiponectin-mediated effects on lipid metabolism in high-fat diet mice
... This fruit is found mainly in the northern region of Brazil and has great antioxidant capacity, mainly due to the large amount of anthocyanins and flavonoids [3]. Studies state that the consumption of açai is an important strategy to mitigate the impairments related to NAFLD, since it reduces inflammation [4] and oxidative stress [5], augments insulin sensitivity [6] and has hypocholesterolemic effects [7]. ...
... These values are substantially superior to those used by our group in previous studies with filtrate açai pulp where total polyphenols range from 118.13 to 458.60 mg (eq. Gallic acid/100 g) and anthocyanins from 6.45 to 31.0 mg/100 g [6,7]. ...
... In the current study, the high-fat diet generated hepatomegaly, elevated lipid macro-and microvesicles, and activity of the serum ALT and AST enzymes. These data corroborate those in previous studies carried out using this model of NAFLD induction [5,6]. The animals in the exercised groups, either with (HAT) or without (HT) açai consumption had a reduced degree of macrovesicular steatosis to similar extents, which means that the main effects were from the exercise. ...
IntroductionNon-alcoholic fatty liver disease (NAFLD) is a metabolic condition that comprises a spectrum of liver diseases. Non-pharmacological treatments such as functional food consumption and aerobic exercise training (AET) have been recommended.Objective
To evaluate the combined effects of açai pulp consumption and AET on the development of NAFLD induced by a high-fat diet.Methods
Male Fischer rats received either standard or high-fat diet. Animals (21.8% lard and 1% cholesterol) were treated with lyophilized açai pulp (1%), AET or açai plus AET for 8 weeks. Exercise capacity, body fat, serum metabolites (triacylglycerol, total cholesterol, and high-density lipoprotein) and enzymes (lipase, aspartate aminotransferase and alanine aminotransferase), liver macrovesicular steatosis and liver lipid peroxidation (thiobarbituric acid reactive substances—TBARS) were evaluated.ResultsAçai consumption reduced the levels of serum total cholesterol (p = 0.0185). AET with or without açai consumption increased the exercise capacity (p = 0.0097) and reduced body fat (p = 0.0001) similarly. Both AET and açai consumption individually reduced the concentrations of aspartate aminotransferase (p = 0.0103) and TBARS (p = 0.0014). AET with or without açai consumption reduced the degree of macrovesicular steatosis (p < 0.0001) likewise.ConclusionsAçai consumption or AET protect against increases in serum metabolite (total cholesterol) and enzyme (aspartate aminotransferase) and liver lipid peroxidation (TBARS), whereas AET prevents increases in the degree of macrovesicular steatosis in this model of NAFLD induced by high-fat diet in rats. The combination of treatments, nevertheless, does not provide additional effects.
... Consumption of a high fat diet causes increasing body weight and enlargement of internal organs, including the liver, as well as dyslipidemia and obesity in rats [7][8][9]. Feeding high fat diet to rats were able to attribute characteristics hypercholesterolemia which is relevance to human biology [8][9][10][11][12]. A high fat diet was therefore an option in this study. ...
... The health benefits include improved regulation of blood sugar levels, action against hypercholesterolemia and reduced risk for cardiovascular disease due to the antioxidant properties [15,16]. Previous reports suggest that fruits rich in flavonoids and phenolic acids have been shown to improve the features of NAFLD, such as oxidative stress, dyslipidemia, liver steatosis, and inflammation in rodents [10][11][12]. Our previous study reported the health benefits of Maoberry around four to sixteen portions a day could against in hypercholesterolemia and progression of cardiac tissue deterioration in rats [8,9]. ...
... Similar to our study, in a clinical study of 20 patients with metabolic syndrome, Kargiotis et al. [29] found that STAT monotherapy (10 mg/day) showed reduced liver steatosis on liver ultrasonography and biopsy within 12 months of treatment. In addition, previous studies have shown that supplementation of fruit extracts that mainly contained polyphenol substances (including rutin, myricetin, morin and quercetin), such as acai berry and mulberry fruit, improved the pathology of liver steatosis in rats and mice fed high fat diets [11,30,31]. Moreover, liver TG levels in the rats were significantly decreased with Maoberry extract in MH groups as well. ...
Abstract Backgound Obesity and dyslipidemia are major risk factors associated with non-alcoholic fatty liver disease (NAFLD). NAFLD refers to the accumulation of fat in more than 5% of the liver without alcohol consumption. NAFLD is the most common liver disease and is rapidly becoming a global public health problem. Maoberry (Antidesma bunius) is a fruit rich in antioxidants, especially phenolic compounds, which are reported to have benefits for patients with NAFLD. Methods We evaluated the effect of Maoberry extract on fat metabolism in liver tissues of high fat diet–induced rats. Five (5) groups (n = 12) of male Sprague-Dawley (SD) rats were divided into those given a high fat diet with no treatment (HF), different dosages of Maoberry extracts (0.38 [ML], 0.76 [MM) and 1.52 [MH] g/kg body weight) and 10 mg/kg statin (STAT). The rats were fed a high fat diet for 4 weeks to induce obesity and subsequently continued more for 12 weeks with treatments of Maoberry extracts or STAT. The levels of triglyceride, liver enzymes, oxidative stress and inflammation markers, triglyceride synthesis regulators, and pathology of the liver in high fat diet-induced rats were investigated. Results Feeding Maoberry extract in MH groups resulted in decreasing levels of serum alanine aminotransferase (ALT), liver triglyceride, liver thiobarbituric acid reactive substances (TBARS) and mRNA expression of tumour necrosis factor (TNF)-α, interleukin (IL)-6, glycerol-3-phosphate acyltransferase (GPAT)-1 and acetyl-coenzyme A carboxylase (ACC) compared with the HF group (P
... In vivo studies demonstrate the action of açai in improving the lipid profile, different parameters related to oxidative stress, antioxidant enzymes and the reduction of non-alcoholic liver steatosis (11)(12)(13)(14). In addition to acting as an antioxidant, anthocyanins also regulate the lipid metabolism, and we have previously shown that açai attenuates the development of hepatic steatosis in mice on a high-fat diet, downregulating the expression of genes involved in lipogenesis (15). ...
... We examined whether açai improves liver damage, antioxidant enzymes and inflammation in fructose rich diet-induced NAFLD in rats. Although there are other reports on positive effects of açai on steatosis induced by a high-fat diet as well as its antioxidant capacity (11)(12)(13)(14)(15), studies using açai on steatosis induced by fructose were not found. We provide evidence that the açai fruit reduced lipid accumulation, inflammation and oxidative stress in rats with NAFLD induced by a fructose-rich diet. ...
... The presence of açai in the FA group did not change body weight gain and fecal excretion; the same behavior was observed in studies using açai in high-fat model (11,15). In addition, the açai treatment did not modify food consumption. ...
Introduction:
A large evidence-based reports a J-shaped association among moderate alcohol consumption and cardiovascular health. Low-moderate alcohol intake has been related to lower all-cause mortality (20%) and ischemic heart events (40%) compared to abstainers. The dose that is allegedly beneficial varies between 10-20 gr/day for women and men respectively. Moreover, the drinking pattern seems to be significant in order to get healthy effects. Moderate alcohol consumption hinders atherogenesis by several mechanisms mainly improving lipid profile and reducing thrombogenesis. Nevertheless, it is still unclear whether high-polyphenol alcoholic beverages, such as wine and beer, confer a greater cardiovascular protection than spirits, which have much less polyphenol content.
... Açaí (Euterpe oleracea Martius), an Amazon fruit, with a high content of phenolic compounds of the class of anthocyanins, mainly cyanidin-3-rutinoside, cyanidin-3-glycoside, cyanidin-3-sambubioside, peonidin-3-glycoside and peonidin-3-rutinoside [22] has been the subject of research seeking to evaluate its potential beneficial effect on health. Recent work evaluating the effect of açaí on NAFLD pathology demonstrated a hepatoprotective action of this fruit by modulating the expression of genes involved in adiponectin signaling, lipogenesis and oxidation of fatty acids [23,24]. However, little is known about the effect of açaí on the molecular mechanisms involving hepatic and lipid metabolism in NAFLD induced by high-fat maternal diet and its effect on offspring. ...
... Animals were divided into four groups receiving different diets: control diet (C), high-fat diet (HF, 60% of total calories as fat, been 53% saturated fat, 6% soybean oil and 1% cholesterol), control diet supplemented with açaí pulp (CA, control diet plus 2% of açaí pulp) or high-fat diet supplemented with 2% of açaí pulp (HFA). Control diet and high-fat diet were based on the AIN-93G diet, with some modifications according to previous studies [23,[27][28][29]. All animals were maintained in a standard environment, 23 °C ± 2 °C, 55% humidity and 12-h light/darkness cycle, with food and water provided ad libitum. ...
... In view of the role of UCP2 in reducing ROS and promoting efficient mitochondrial oxidation, an increase in Ucp2 expression could suggest an increase in the beta oxidation of fatty acids in P21. In fact, a study evaluating the effect of açaí aqueous extract on hepatic steatosis in adults mice showed an increase in carnitine-palmitoyl transferase (CPT-I), a key enzyme in the entry of fatty acids to β-oxidation [23]. In addition, uncoupling proteins also carry the transport of fatty acid anions and lipoperoxide anions through the inner mitochondrial membrane [17]. ...
Purpose
Maternal high-fat diet affects offspring and can induce metabolic disorders such as non-alcoholic fatty liver disease (NAFLD). New therapeutic strategies are being investigated as way to prevent or attenuate this condition. The objective of this study was to evaluate the effect of açaí supplementation in the maternal high-fat diet on dams and offspring lipid metabolism.
Methods
Female Fisher rats were divided in four groups and fed a control diet (C), a high-fat diet (HF), an açaí supplemented diet (CA) and a high-fat diet supplemented with açaí (HFA) 2 weeks before mating, during gestation and lactation. The effects of açaí were evaluated in the male offspring after birth (P1) and weaning (P21).
Results
HFA reduced relative liver weight, fat and cholesterol liver content in dams and improved liver steatosis as confirmed by histological analyses. HFA increased serum cholesterol and expression of Srebpf1 and Fasn genes. In offspring, HFA decreased relative liver weight, and serum cholesterol only in P21. An increase in the Sirt1, Srebpf1 and Fasn genes expression was observed in P21.
Conclusions
These results suggest that açaí supplementation may attenuate NAFLD in dams and protect offspring from the detrimental effects of lipid excess from a maternal high-fat diet.
... Numerous studies have described the actions of anthocyanins in the regulation of lipid metabolism and inflammation; however, the doses, in most cases, are impractical for a normal human diet. Therefore, we conducted this investigation using the format (AAE) and dosing of açai that was previously employed by Guerra, et al. 17 to estimate physiological levels of consumption that could be easily ingested with a normal diet. ...
... To facilitate subsequent in vivo analyses, the açai, as a natural and safe source, was used, and the dose managed was the same as that used by Guerra,et al. 17 in an animal model capable of exerting a protective effect against NAFLD. In comparison, the average human dose of daily intake for açai would be approximately 200 g for a 70 kg individual, corresponding to approximately 3 g/kg body weight 17 . Notably, the consumption of açai has also previously been shown to have beneficial effects on insulin resistance in overweight individuals 23 . ...
... Additionally, these changes, which can be caused by HF diets, increased the production pattern and secretion of proinflammatory cytokines, such as TNF-α. Thus, our study complements the findings by Guerra, et al. 17 , which showed that this model exhibited an intense accumulation of triglycerides in the liver, lipid deposition, and significant increase in the steatosis score. ...
Non-alcoholic fatty liver disease (NAFLD), the most predominant liver disease worldwide, is a progressive condition that encompasses a spectrum of disorders ranging from steatosis to steatohepatitis, and, ultimately, cirrhosis and hepatocellular carcinoma. Although the underlying mechanism is complex and multifactorial, several intracellular events leading to its progression have been identified, including oxidative stress, inflammation, mitochondrial dysfunction, apoptosis, and altered endoplasmic reticulum (ER) homeostasis. Phenolic compounds, such as those present in açai (Euterpe oleracea Mart.), are considered promising therapeutic agents due to their possible beneficial effects on the prevention and treatment of NAFLD. We tested in vitro effects of aqueous açai extract (AAE) in HepG2 cells and its influence on oxidative stress, endoplasmic reticulum stress, and inflammation in a murine model of high fat diet-induced NAFLD. In vitro AAE exhibited high antioxidant capacity, high potential to inhibit reactive oxygen species production, and no cytotoxicity. In vivo, AAE administration (3 g/kg) for six weeks attenuated liver damage (alanine aminotransferase levels), inflammatory process (number of inflammatory cells and serum TNFα), and oxidative stress, through the reduction of lipid peroxidation and carbonylation of proteins determined by OxyBlot and modulation of the antioxidant enzymes: glutathione reductase, SOD and catalase. No change was observed in collagen content indicating an absence of fibrosis, stress-related genes in RE, and protein expression of caspase-3, a marker of apoptosis. With these results, we provide evidence that açai exhibits hepatoprotective effects and may prevent the progression of liver damage related to NAFLD by targeting pathways involved in its progression.
... In vivo studies demonstrate the action of açai in improving the lipid profile, different parameters related to oxidative stress, antioxidant enzymes and the reduction of non-alcoholic liver steatosis (11)(12)(13)(14). In addition to acting as an antioxidant, anthocyanins also regulate the lipid metabolism, and we have previously shown that açai attenuates the development of hepatic steatosis in mice on a high-fat diet, downregulating the expression of genes involved in lipogenesis (15). ...
... We examined whether açai improves liver damage, antioxidant enzymes and inflammation in fructose rich diet-induced NAFLD in rats. Although there are other reports on positive effects of açai on steatosis induced by a high-fat diet as well as its antioxidant capacity (11)(12)(13)(14)(15), studies using açai on steatosis induced by fructose were not found. We provide evidence that the açai fruit reduced lipid accumulation, inflammation and oxidative stress in rats with NAFLD induced by a fructose-rich diet. ...
... The presence of açai in the FA group did not change body weight gain and fecal excretion; the same behavior was observed in studies using açai in high-fat model (11,15). In addition, the açai treatment did not modify food consumption. ...
Introduction:
the excessive consumption of fructose can cause liver damage, characteristic of non-alcoholic fatty liver disease (NAFLD) associated with changes in lipid metabolism and antioxidant defenses. Açai, the fruit of Euterpe oleraceaMart., has demonstrated numerous biological activities, including anti-inflammatory, antioxidant, and lipid metabolism modulating action.
Objective:
we evaluated the benefits of açai supplementation on liver damage caused by replacing starch with fructose in rats.
Methods:
thirty male Fischerrats were divided into two groups, the control group (C, 10 animals), which consumed a standard diet (AIN-93M), and the fructose (F, 20 animals) group, which consumed a diet containing 60% of fructose. After eight weeks, 10 animals from the fructose group received 2% of lyophilized açai, and were called the açai fructose group (FA). The animals were fed ad libitumwith these diets for another ten weeks. Serum, hepatic and fecal lipid profile, antioxidant enzymes and carbonylated protein were assessed and histopathological characterization of the liver was performed.
Results:
açai promoted the reduction of ALT activity in relation to the fructose group (F), reduced alkaline phosphatase to a level similar to that of the control group (C) in relation to the fructose group (F), and reduced catalase activity. The fruit also increased the ratio of total/oxidized glutathione (GSH/GSSG) and reduced the degree of macrovesicular steatosis and the number of inflammatory cells.
Conclusion:
the replacement of starch by fructose during this period was effective in promoting NAFLD. Açai showed attenuating effects on some markers of hepatic steatosis and inflammation.
... In vivo studies demonstrate the action of açai in improving the lipid profile, different parameters related to oxidative stress, antioxidant enzymes and the reduction of non-alcoholic liver steatosis (11)(12)(13)(14). In addition to acting as an antioxidant, anthocyanins also regulate the lipid metabolism, and we have previously shown that açai attenuates the development of hepatic steatosis in mice on a high-fat diet, downregulating the expression of genes involved in lipogenesis (15). ...
... We examined whether açai improves liver damage, antioxidant enzymes and inflammation in fructose rich diet-induced NAFLD in rats. Although there are other reports on positive effects of açai on steatosis induced by a high-fat diet as well as its antioxidant capacity (11)(12)(13)(14)(15), studies using açai on steatosis induced by fructose were not found. We provide evidence that the açai fruit reduced lipid accumulation, inflammation and oxidative stress in rats with NAFLD induced by a fructose-rich diet. ...
... The presence of açai in the FA group did not change body weight gain and fecal excretion; the same behavior was observed in studies using açai in high-fat model (11,15). In addition, the açai treatment did not modify food consumption. ...
Introduction:
the excessive consumption of fructose can cause liver damage, characteristic of non-alcoholic fatty liver disease (NAFLD) associated with changes in lipid metabolism and antioxidant defenses. Açai, the fruit of Euterpe oleracea Mart., has demonstrated numerous biological activities, including anti-inflammatory, antioxidant, and lipid metabolism modulating action.
Objective:
we evaluated the benefits of açai supplementation on liver damage caused by replacing starch with fructose in rats.
Methods:
thirty male Fischer rats were divided into two groups, the control group (C, 10 animals), which consumed a standard diet (AIN-93M), and the fructose (F, 20 animals) group, which consumed a diet containing 60% of fructose. After eight weeks, 10 animals from the fructose group received 2% of lyophilized açai, and were called the açai fructose group (FA). The animals were fed ad libitum with these diets for another ten weeks. Serum, hepatic and fecal lipid profile, antioxidant enzymes and carbonylated protein were assessed and histopathological characterization of the liver was performed.
Results:
açai promoted the reduction of ALT activity in relation to the fructose group (F), reduced alkaline phosphatase to a level similar to that of the control group (C) in relation to the fructose group (F), and reduced catalase activity. The fruit also increased the ratio of total/oxidized glutathione (GSH/GSSG) and reduced the degree of macrovesicular steatosis and the number of inflammatory cells.
Conclusion:
the replacement of starch by fructose during this period was effective in promoting NAFLD. Açai showed attenuating effects on some markers of hepatic steatosis and inflammation.
... Most of the beneficial effects of açai are attributed to secondary metabolites such as flavonoids and other polyphenols, including anthocyanins and proanthocyanidins (specifically cyanidin-3-glucoside and cyanidin-3-rutinoside), which provide antioxidant activity [34,35]. Previous in vitro and animal model studies showed that açai consumption slows the progression of oxidative stress [36,37] and induces hypocholesterolemic [38], antiatherogenic, anti-inflammatory [39], and hepatoprotective [40] effects. Previous work from our laboratory showed that diet supplementation with açai increased serum activity of the antioxidant enzyme PON1 in rats [19] but did not evaluate the effect of açai on the expression of PON isoforms. ...
... However, that study did not assess the expression of PON isoforms. In mice, Guerra et al. [40] demonstrated that administration of açai extract reduced hepatic steatosis by modulation of pathways related to hepatic lipid metabolism but did not evaluate possible effects on antioxidant enzymes. ...
... We also found a negative correlation between serum PON1 activity and progression of steatosis in rats receiving açai pulp. Our results corroborate the report of Guerra et al. [40] and therefore strengthen the hypothesis that açai acts by retarding oxidative stress-associated liver damage induced by HF diet. ...
Açai ( Euterpe oleracea Mart.), a fruit from the Amazon region, has emerged as a promising source of polyphenols. Açai consumption has been increasing owing to ascribed health benefits and antioxidant properties; however, its effects on hepatic injury are limited. In this study, we evaluated the antioxidant effect of filtered açai pulp on the expression of paraoxonase (PON) isoforms and PON1 activity in rats with nonalcoholic fatty liver disease (NAFLD). The rats were fed a standard AIN-93M (control) diet or a high-fat (HF) diet containing 25% soy oil and 1% cholesterol with or without açai pulp (2 g/day) for 6 weeks. Our results show that açai pulp prevented low-density lipoprotein (LDL) oxidation, increased serum and hepatic PON1 activity, and upregulated the expression of PON1 and ApoA-I in the liver. In HF diet-fed rats, treatment with açai pulp attenuated liver damage, reducing fat infiltration and triglyceride (TG) content. In rats receiving açai, increased serum PON1 activity was correlated with a reduction in hepatic steatosis and hepatic injury. These findings suggest the use of açai as a potential therapy for liver injuries, supporting the idea that dietary antioxidants are a promising approach to enhance the defensive systems against oxidative stress.
... The use of açaí increased the production and effectiveness of adiponectin, improving insulin sensitivity and increasing PPAR-α-mediated fatty acid oxidation [116] The extract significantly suppressed the establishment and growth of endometriosis [139] Dried açaí Açaí-enriched diet Male Wistar rats ...
... Moreover, açaí increased the lifespan of females subjected to oxidative stress, suggesting that açaí improves survival [159]. Açaí may be an effective antagonist of the deleterious effects of high-fat diets and oxidative stress, which accelerate the aging process [87,[115][116][117]158,159]. ...
The açaí palm (Euterpe oleracea Mart.), a species belonging to the Arecaceae family, has been cultivated for thousands of years in tropical Central and South America as a multipurpose dietary plant. The recent introduction of açaí fruit and its nutritional and healing qualities to regions outside its origin has rapidly expanded global demand for açaí berry. The health-promoting and disease-preventing properties of this plant are attributed to numerous bioactive phenolic compounds present in the leaf, pulp, fruit, skin, and seeds. The purpose of this review is to present an up-to-date, comprehensive, and critical evaluation of the health benefits of açaí and its phytochemicals with a special focus on cellular and molecular mechanisms of action. In vitro and in vivo studies showed that açaí possesses antioxidant and anti-inflammatory properties and exerts cardioprotective, gastroprotective, hepatoprotective, neuroprotective, renoprotective, antilipidemic, antidiabetic, and antineoplastic activities. Moreover, clinical trials have suggested that açaí can protect against metabolic stress induced by oxidation, inflammation, vascular abnormalities, and physical exertion. Due to its medicinal properties and the absence of undesirable effects, açaí shows a promising future in health promotion and disease prevention, in addition to a vast economic potential in the food and cosmetic industries.
... Extractos metanólicos de pulpa de açaí colombiano muestran capacidad antioxidante in vitro inhibiendo los radicales ABTS y DPPH con valores de 24,7 y 21,049 µmol Trolox Equivalente (TE)/100 g respectivamente (8), estos valores son mayores a los reportados en muestras de açaí de Brasil con valores de 2,78 y 13,340 µmol TE/100 g, para ABTS y DPPH respectivamente (8). La administración de extractos acuosos ricos en antocianinas de pulpa de açaí (3 g/kg) en ratas Wistar alimentadas con dietas altas en grasas reduce el contenido de triglicéridos totales en hígado (44%) y una atenuación de la esteatosis hepática del 80% (9). Además, el açaí posee propiedades antiinflamatorias, como lo muestran Machado et al. (10) 20, v/v) de caqui en ratas Wistar con artritis inducida, mediante la inyección intradérmica de una emulsión de colágeno bovino tipo II. ...
... La administración oral de extractos acuosos de açaí en ratas con dietas altas en grasa, reducen los triglicéridos del hígado y atenúan la esteatosis hepática, lo cual se asoció con la regulación positiva mediada por los compuestos fenólicos del extracto de los genes involucrados en la señalización de adiponectina, incluido el receptor 2 de adiponectina, PPAR-α, y su gen diana, carnitina palmitoiltransferasa (9). Por otra parte, la administración de extractos acuosos de pulpa de pitaya blanca, mejoró la resistencia a la insulina inducida por una dieta alta en grasas, la esteatosis hepática y la hipertrofia adiposa por medio de la regulación de la expresión de genes involucrados en el metabolismo de lípidos y colesterol (Srebp1, HMGCoR, Cpt1b, HL, Insig1 e Insig2) y el aumento de la hormona FGG21 producida por el hígado como respuesta a la ingesta de grasa, migrando a la grasa parda y produciendo un gran aumento de gasto energético y sus genes (Klb, FGFR2, Egr1 y cFos) (40). ...
Los déficits nutricionales en la mujer deportista causan numerosos problemas de salud, así como un empeoramiento en el rendimiento deportivo, como consecuencia de estas deficiencias nutricionales. El conocimiento de estos déficits y su prevención deben ser un aspecto principal para cualquier responsable deportivo. Establecer la importancia del estudio de los déficits de energía, proteínas, minerales (Fe, Ca y Mg) y vitaminas (Vitamina D, ácido fólico y vitamina B12) que pueden desarrollar las mujeres deportistas y su relación con la prevalencia de la tríada femenina y constatar la importancia del conocimiento por parte de los responsables deportivos de los problemas derivados de los déficits nutricionales. Se realizó una búsqueda bibliográfica de artículos, entre 2013-2020, relevantes para el objetivo de estudio. Se usaron bases de datos científicas como PubMed y Pennutrition, siguiendo los criterios de exclusión e inclusión elegidos para este estudio. 51 artículos fueron encontrados. Los resultados mostraron la prevalencia de energía, Fe, vitamina D y Ca, así como un suficiente aporte proteico, faltan estudios para determinar los niveles de vitamina B12 y ácido fólico. Se observó, además la prevalencia de mujeres que cumplen con uno o varios factores de riesgo para el desarrollo de la tríada de la deportistas femenina. Es imprescindible la prevención o, el tratamiento, de los déficits nutricionales en las mujeres deportistas para asegurar un correcto estado de salud y un rendimiento deportivo óptimo.
... Açaí has a concentration of polyunsaturated (PUFA) and monounsaturated (MUFA) fatty acids of approximately 60% that can regulate lipid metabolism, while polyphenols mainly from the anthocyanin class, can contribute to neutralise free radicals [19]. Studies have shown that introduction of açaí in a high-fat diet is able to prevent the development of NAFLD via adiponectin mediation [20] and avoid the progression of liver damage by controlling oxidative stress [21]. Recently, our group demonstrated that the addition of açaí in the maternal diet can also attenuate the accumulation of lipids in the liver, reducing the progression of NAFLD in dams and protecting the offspring against a more harmful metabolic outcome [22]. ...
... The composition of these experimental diets was based on AING-93G proposed by Reeves et al., 1993 [23] and are presented in Table 1. The values of lard and cholesterol were defined from previously published studies [20,24]. Supplementation with 2% açaí pulp (2 g/kg diet) was based on previous experimental work [17]. ...
Lipids excess from an uterine environment can increase free radicals production of and thus induce oxidative status imbalance, a key factor for progression of non-alcoholic fatty liver disease (NAFLD) in offspring. Food antioxidant components in maternal diet may play an important role in preventing offspring metabolic disorders. The objective of the study was to evaluate the effects of açaí pulp supplementation on maternal high-fat diet, by assessing activity and expression of antioxidant enzymes and biomarkers of oxidative stress in the liver. Female Fisher rats were divided into four groups and fed a control diet (C), a high-fat diet (HF), a control diet supplemented with açaí (CA) and a high-fat diet supplemented with açaí (HFA) before mating, during gestation and lactation. The effects of açaí supplementation on oxidative stress biomarkers and antioxidant enzymes expression were evaluated in dams and male offspring after weaning. HFA diet increased body weight in dams, however reduced absolute and relative liver weight. There was a reduction in liver biomarkers of oxidative stress, malondialdehyde and carbonyl protein, as well as in catalase, glutathione peroxidase and superoxide dismutase activity. In offspring, HFA diet reduced liver weight and increased Gpx1, Gpx4 and Sod1 mRNA expression. These results suggest that açaí is able to restore redox status, preventing oxidative damage in dams by a direct mechanism and to promote beneficial effects on expression of antioxidant defences related genes in offspring.
... A single AB pulp dose enhanced plasma antioxidant capacity 7-fold 3 h after its consumption. Plasma anthocyanins reached maximum levels 2.2 h after AB pulp consumption [179,180]. In another in vivo study, AB pulp supplementation in oxidatively damaged mutant Drosophila melanogaster, in combination with HFD, reversed HFD-induced oxidative stress damage and prolonged the lifespan expectancy by 22% [172,308]. ...
... Intensive feeding with freeze-dried AB pulp attenuated HFD-induced hepatic steatosis by improving IR, adiponectin expression, adiponectin receptor 2, SREBP-1c, PPAR-α, and its target gene, CPT. Fat accumulating gene expression including UCP-2 and fatty acid translocase were reduced by AB treatment [179]. Both lipid accumulation and oxidation were reduced in zebrafish fed with a high-cholesterol diet, and reduced serum TC, LDL-C, and MDA levels were observed in AB-treated zebrafish [171]. ...
Berries are considered "promising functional fruits" due to their distinct and ubiquitous therapeutic contents of anthocyanins, proanthocyanidins, phenolic acids, flavonoids, flavanols, alkaloids, polysaccharides, hydroxycinnamic, ellagic acid derivatives, and organic acids. These polyphenols are part of berries and the human diet, and evidence suggests that their intake is associated with a reduced risk or the reversal of metabolic pathophysiologies related to diabetes, obesity, oxidative stress, inflammation, and hypertension. This work reviewed and summarized both clinical and non-clinical findings that the consumption of berries, berry extracts, purified compounds, juices, jams, jellies, and other berry byproducts aided in the prevention and or otherwise management of type 2 diabetes mellitus (T2DM) and related complications. The integration of berries and berries-derived byproducts into high-carbohydrate (HCD) and high-fat (HFD) diets, also reversed/reduced the HCD/HFD-induced alterations in glucose metabolism-related pathways, and markers of oxidative stress, inflammation, and lipid oxidation in healthy/obese/diabetic subjects. The berry polyphenols also modulate the intestinal microflora ecology by opposing the diabetic and obesity rendered symbolic reduction of Bacteroidetes/Firmicutes ratio, intestinal mucosal barrier dysfunction-restoring bacteria, short-chain fatty acids, and organic acid producing microflora. All studies proposed a number of potential mechanisms of action of respective berry bioactive compounds, although further mechanistic and molecular studies are warranted. The metabolic profiling of each berry is also included to provide up-to-date information regarding the potential anti-oxidative/antidiabetic constituents of each berry.
... (the specific isoform found in the liver), and PPARα, showing increased β-oxidation via adiponectin-mediated up-regulation of PPARα [243]. Moreover, resveratrol delivered orally at 30 mg/kgbw for 6 weeks enhanced hepatic activity of acyl-CoA oxidase and CPT1A in rats fed a high-fat diet [45]. ...
... Although numerous studies report increased expression of PPARα in fatty liver disease, others are in accordance with our results observing unchanged or even less expression of PPARα in NAFLD [4,48]. Polyphenols also had little effect on PPARα expression in the current study, in contrast to some studies in rodents fed polyphenols with a highfat diet [95,243]. Some polyphenols such as cyanidin may be an agonist and a natural ligand for different PPARs [245], and therefore may affect PPAR activity without affecting expression. ...
Non-alcoholic fatty liver disease (NAFLD) is a public health burden. Steatosis as the “first hit”, and oxidative stress, inflammation, mitochondrial dysfunction, and endoplasmic reticulum stress as the “second hits” are the main contributors of the progression of fatty liver to non-alcoholic steatohepatitis (NASH). Dietary polyphenols have shown promise in protecting the liver against NAFLD. The relative effectiveness and mechanisms of different polyphenols however is mostly unknown. In this thesis HepG2 hepatocytes exposed to oleic or palmitic acid were used as a model system to explore the ability of selected polyphenols (resveratrol, quercetin, catechin, cyanidin, cyanidin-3-glucoside, berberine) from different classes to protect against molecular aspects of NAFLD and NASH. In an investigation of the “first hit” (Chapter 3), different polyphenols protected similarly against oleic acid-induced intracellular lipid accumulation, but differed in their effects on the expression of genes and proteins involved in lipogenesis, fatty acid oxidation, mitochondrial biogenesis, and bioenergetics. In an investigation of “second hits” (Chapter 4), most of the polyphenols decreased reactive oxygen species (ROS), prevented the decrease in uncoupling protein 2 (UCP2) mRNA, prevented the increase in tumor necrosis factor alpha (TNFα) mRNA, reversed decreases in mitochondrial biogenesis and increased expression of mitochondrial respiratory complexes and manganese superoxide dismutase (MnSOD). The anthocyanins were unique in decreasing ROS without inducing mitochondrial biogenesis or Mn-SOD mRNA expression. In investigations with palmitic acid (Chapter 5), exposure of HepG2 cells to palmitic acid induced endoplasmic reticulum (ER) stress evidenced by upregulated mRNA for the ER chaperones glucose-regulated protein 94 and 78 (GRP94, GRP78) and oxygen-regulated protein 150 (ORP150), cochaperone endoplasmic reticulum-localized DnaJ homologue 4 (ERdj4), and proapoptotic CCAAT-enhancer-binding protein homologous protein (CHOP). A few of the polyphenols (quercetin, catechin, cyanidin) protected against these changes. In a comparison of flavonoids with their phenolic breakdown/digestion products (Chapter 6), the polyphenols 2,4,6-trihydroxybenzaldehyde, protocatechuic acid, and caffeic acid protected similarly to quercetin and cyanidin against oleic and palmitic acid-induced steatosis and ROS generation. Moreover, in a short-term 1 h exposure (to limit spontaneous degradation in the medium), only breakdown/digestion products prevented an oleic acid-induced decrease of mitochondrial biogenesis. In conclusion, different classes of dietary polyphenols were all able to protect against steatosis and ROS generation in this in vitro model of NAFLD. Part of the mechanism for some polyphenols was through effects on mitochondrial biogenesis and function, bioenergetics, and ER stress. Phenolic breakdown/digestion products of flavonoids were shown to contribute to the protective effects of parent polyphenols.
... As a result, foods containing bioactive compounds, especially fruits, have been widely used in the prevention and treatment of chronic diseases, including NAFLD [9,10]. Consistent with the above findings, previous in vitro and in vivo studies have demonstrated that fruits with high phenolic content act as therapeutic agents against hepatic damage during the initial stages of NAFLD [10,11,12]. ...
Bioactive compounds, present in some foods, act enhancing the endogenous antioxidant system and are proposed as an effective strategy in preventing the changes induced by free radicals in some diseases, such as nonalcoholic fatty liver disease (NAFLD). There has been an increase in the number of studies carried out with the aim of finding natural antioxidant compounds present in fruits, mainly the native fruits of Brazil, because they contain a high content of these compounds. Araç á (Psidium cattleianum Sabine) is a fruit that is rich in polyphenols and exhibits strong antioxidant, antiproliferative, and anti-inflammatory activities. Therefore, the present study investigated the effects of araç á flour on oxidative stress, liver injury, and antioxidant defenses in high-fat diet-induced hepatic steatosis in rats. In vitro experiments showed that araç á contains high concentrations of total polyphenols and exhibits strong antioxidant activity with no cytotoxicity. In vivo experiments indicated that the addition of araç á to a high-fat diet inhibited the activities of alanine aminotransferase and aspartate enzymes, reduced macrovesicular steatosis, increased the paraoxonase activity, and increased the concentration of the total and reduced forms of glutathione. Therefore, our findings suggested the hepatoprotective role of araç á against the progression of steatosis.
... The consumption of high-fat diets has been shown to contribute to the development of hyperlipidemia and glucose intolerance [50]. In the present study, hyperglycemia was demonstrated in the groups supplemented with ethanolic or aqueous extract of G. gardneriana, regardless of dose. ...
The study of medicinal plants, such as the genus Garcinia (Clusiaceae), in the treatment of non-communicable chronic diseases has aroused the interest of researchers. However, there are no studies in the literature that have investigated the effects of Garcinia gardneriana in experimental models of obesity for possible metabolic alterations. Swiss mice receiving a high-fat diet were supplemented with aqueous or ethanolic extract of G. gardneriana at doses of 200 or 400 mg/kg/day. It was found that there was a reduction in food consumption in experimental groups compared with the control groups, and the group supplemented with aqueous extract at a dose of 200 mg/kg/daydisplayed a reduction in weight. The results showed an increase in the values of high density lipoprotein (HDL-c), total cholesterol, triglycerides and fasting blood glucose. G. gardneriana did not protect against insulin resistance, and caused in an increase in monocyte chemoattractant protein-1 (MCP-1) concentrations and a reduction in interleukin 10 (IL-10). In addition, hepatic steatosis and microvesicular steatosis were indicated. It was revealed that, under the experimental conditions in the study, G. gardneriana did not prevent weight gain or comorbidities; that is, a different behavior was obtained from that described in the literature with regard to the medicinal potential of the Garcinia species, which is probably related to the phytochemical properties.
... The C3G anthocyanin was once reported to stimulate the expression of adiponectin by the adipose tissue probably because of its involvement in the acetylation of FoxO1, which is a transcription factor that regulates adiponectin production [42]. A study has demonstrated that the treatment of obese mice with açai aqueous extract (3 g kg −1 ) also attenuated insulin resistance and ameliorated adiponectin levels in serum with no alteration in body weight gain, corroborating our results [43]. Furthermore, as shown, açai has oleic acid as the major fatty acid. ...
Scope
Obesity and insulin resistance constitute risk factors for the development of tauopathies and other neurodegenerative diseases. (Poly)phenol compounds are under study for its role in protecting effects against neural injuries and degeneration. Here, we investigated the effect of Amazonian açai pulp (AP) intake in the prevention of memory and cognitive impairment resulting from a high-fat diet intake in mice.
Methods and results
Obesity and insulin resistance was induced with a high-fat diet and supplemented with 2% AP to investigate peripheral insulin resistance, recognition memory and tau protein stability via AKT/GSK3-β signaling pathway. The consumption of AP for 70 days improved peripheral insulin sensitivity and phosphorylation of AKT/GSK3-β in mice hippocampi. The animals fed high-fat diets supplemented with AP showed better performance in the novel object recognition test (NOR) in comparison to the H group. Catalase activity and reduced glutathione (GSH) values were improved in the treated mice.
Conclusions
These results suggest that the supplementation of AP can attenuate the effects of high-fat diet consumption in peripheral insulin resistance and improve cognitive behavior.
... According to the manufacturers' instructions, blood insulin and glycation (AGE) were measured using commercial kits enzyme-linked assay (ELISA). The Guerra et al. [33] equation was used to construct the homeostasis model evaluation of β-cell function (HOMA-). High-density lipoprotein (HDL), low-density lipoprotein (LDL), blood urea nitrogen (BUN), serum triglyceride (TG), total cholesterol (TC), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione-S-transferase, and levels of creatine were measured using kits obtained from Rawabi Marketing International (RMI, Riyadh, Kingdom of Saudi Arabia). ...
Diabetes kidney damage (DKD) is a chronic inflammatory disease of the kidney induced with continuous hyperglycemia as the most prevalent consequence of diabetes. Washingtonia filifera seed oil (WFO) was used as a traditional medicine to cure various diseases in ancient Saudi. This work was carried out to investigate the potential protective impact of WFO against DKD on streptozotocin (STZ)-induced type 2 diabetic mice (C57BL/6 mice). The mice were randomly split into groups: C, C + WFO (200 mg/Kg B.W.), T2D, and T2D + WFO (200 mg/Kg B.W.). Diabetes was created in mice groups except for the control group after 6 weeks of high-fat diet (HFD) feeding. Treatments with STZ (60 mg/kg body weight) were administered three times for 6 weeks, and after that, mice were sacrificed. Kidney tissues and serum were obtained to analyze levels of insulin, metabolism of lipids [triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and free fatty acids (FFA)], antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)], creatine, and blood urea nitrogen (BUN). In addition, H&E staining had been used to investigate the histological changes of the kidneys. In T2D mice, WFO corrected aberrant serum lipids (TG, TC, HDL, LDL, and FFA), elevated antioxidative enzyme levels (CAT, SOD, and GPx), and inhibited GST to various degrees. In addition, WFO improves kidney pathological traits such as fibrosis of the kidney, hypertrophy of glomeruli, and basement membrane thickness of glomeruli. Through hypoglycemic, hypolipidemic, antioxidative, and anti-inflammatory actions, WFO might ameliorate diabetic alterations in T2D mice. WFO could significantly reduce AGE buildup in the T2D mice kidneys, therefore alleviating kidney oxidative stress and inflammatory kidney damage.
... Naukowcy opisali, że długotrwałe podawanie ekstraktu miało działanie ochronne przeciw otyłości, hipercholesterolemii, hiperglikemii, insulinooporności oraz poprawiało stan śródbłonka naczyń u myszy na diecie wysokotłuszczowej [56]. Wprowadzenie jagód açaí do diety bogatotłuszczowej u myszy zmniejszało też ryzyko powstawania niealkoholowego stłuszczenia wątroby [57]. ...
... Additionally, high-fat mice supplemented with açaí showed attenuated hepatic steatosis via adiponectin-mediated effects on lipid metabolism (Guerra et al., 2015). In humans, supplementation with açaí results in a favorable action on plasma HDL (Pala et al., 2018), a positive impact on the reduction of LDL oxidation with a tendency to increase plasma antioxidant capacity (Sampaio et al., 2006) and a beneficial overall role against atherosclerosis (Feio et al., 2012). ...
One of the more significant challenges for the planet is to secure sufficient food security and nutrition on a worldwide scale. A better and sustainable use of biodiversity is of critical importance and characterization of underused but highly nutritional fruit, and vegetable is a priority. This chapter discusses the functional research of eight Amazonian fruits. Four fruits are from trees, Spondias mombin, Myrciaria dubia, Genipa americana and the well-known Brazilian nut (Bertholletia excelsa). Four fruits from palm trees are described, Astrocaryum vulgare, Mauritia flexuosa, Bactris gasipaes and the well-known açaí (Euterpe oleracea). Amazon fruits and nuts are the most abundant sources of bioactive compounds with antioxidant action, such as phenolic compounds, carotenoids, tocopherols, vitamin C, unsaturated fatty acids (UFA), terpenoids and steroids. Characteristic compounds, present in a higher amount, are a highlight for some fruits, such as vitamin C in camu-camu fruit, carotenoids in the peach palm and tucuma fruits, iridoids in genipap, and selenium and UFA in Brazil nut. The synergistic effect of all these compounds shows clear evidence of the health benefits of the consumption of these fruits associated with their high antioxidant capacity.
... As a regulator of energy balance by affecting whole body fuel utilization, AMPK induces fatty acid oxidation and inhibits adipocyte differentiation and the synthesis of hepatic fatty acid, cholesterol [24] emerging as a key target for obesity resolution. It is also involved in the regulation of adiponectin, which can activate p-AMPK [25]. In line with this result, our study showed a slightly larger increase in the adiponectin level in IG than that in CG; although this difference between the groups was not statistically significant. ...
Recent animal studies found the potential of a collagen peptide derived from skate skin to have anti-obesity effects through the suppression of fat accumulation and regulation of lipid metabolism. However, no studies have yet been performed in humans. Here, this very first human randomized, placebo-controlled, and double-blinded study was designed to investigate the efficacy and tolerability of skate skin collagen peptides (SCP) for the reduction of body fat in overweight adults. Ninety healthy volunteers (17 men) aged 41.2 ± 10.4 years with a mean body mass index of 25.6 ± 1.9 kg/m2 were assigned to the intervention group (IG), which received 2000 mg of SCP per day or to the control group (CG) given the placebo for 12 weeks and 81 (90%) participants completed the study. Changes in body fat were evaluated using dual energy X-ray absorptiometry as a primary efficacy endpoint. After 12 weeks of the trial, the percentage of body fat and body fat mass (kg) in IG were found to be significantly better than those of subjects in CG (−1.2% vs. 2.7%, p = 0.024 and −1.2 kg vs. 0.3 kg, p = 0.025). Application of SCP was well tolerated and no notable adverse effect was reported from both groups. These results suggest the beneficial potential of SCP in the reduction of body fat in overweight adults.
... While many studies have reported upregulated PPARα mRNA in NAFLD, others have similarly observed unchanged or even down-regulated PPARα in NAFLD [11,40]. Polyphenols also had little effect on PPARα expression in the current study, which is in contrast to some studies in rodents fed polyphenols with a high-fat diet [41]. Some polyphenols such as cyanidin may be an agonist and a natural ligand for different PPARs [42] and, therefore, may affect PPAR activity without affecting PPARα mRNA or protein expression. ...
In this study, we aimed to determine the relative effectiveness of common dietary polyphenols or the isoquinoline alkaloid berberine in protecting against molecular mechanisms underlying non-alcoholic fatty liver disease (NAFLD) involving changes to cellular lipid metabolism and bioenergetics. In a model of steatosis using HepG2 hepatocytes, exposure of the cells to 1.5 mM oleic acid (OA) for 24 h caused steatosis and distorted cell morphology, induced the expression of mRNA for enzymes that are involved in lipogenesis and fatty acid oxidation (FAS and CPT1A), and impaired indices of aerobic energy metabolism (PPARγ mRNA expression, mitochondrial membrane potential (MMP), and galactose-supported ATP production). Co-treatment with 10 µM of selected polyphenols all strongly protected against the steatosis and changes in cell morphology. All polyphenols, except cyanidin, inhibited the effects on FAS and PPARγ and further increased CPT1A1 expression, suggesting a shift toward increased β-oxidation. Resveratrol, quercetin, catechin, and cyanidin, however not kuromanin or berberine, ameliorated the decreases in MMP and galactose-derived ATP. Berberine was unique in worsening the decrease in galactose-derived ATP. In further investigations of the mechanisms involved, resveratrol, catechin, and berberine increased SIRT1 enzyme activity and p-AMPKαThr172 protein, which are involved in mitochondrial biogenesis. In conclusion, selected polyphenols all protected against steatosis with similar effectiveness, however through different mechanisms that increased aerobic lipid metabolism and mitochondrial function.
... In contrast, the inhibition of AMPK could increase the accumulation of hepatocellular lipids in hepatocytes [44]. Moreover, AMPK is involved in the regulation of adipokines such as adiponectin and leptin, which can stimulate the phosphorylation of AMPK [45]. In obesity-induced animals, decreased adiponectin levels and increased leptin levels in the plasma have been observed [46]. ...
This study investigated the anti-obesity effects of collagen peptide derived from skate skin on lipid metabolism in high-fat diet (HFD)-fed mice. All C57BL6/J male mice were fed a HFD with 60% kcal fat except for mice in the normal group which were fed a chow diet. The collagen-fed groups received collagen peptide (1050 Da) orally (100, 200, or 300 mg/kg body weight per day) by gavage, whereas the normal and control groups were given water (n = 9 per group). The body weight gain and visceral adipose tissue weight were lower in the collagen-fed groups than in the control group (p < 0.05). Plasma and hepatic lipid levels were significantly reduced by downregulating the hepatic protein expression levels for fatty acid synthesis (sterol regulatory element binding protein-1 (SREBP-1), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC)) and cholesterol synthesis (SREBP-2 and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR)) and upregulating those for β-oxidation (peroxisome proliferator-activated receptor alpha (PPAR-α) and carnitine palmitoyltransferase 1 (CPT1)) and synthesis of bile acid (cytochrome P450 family 7 subfamily A member 1 (CYP7A1)) (p < 0.05). In the collagen-fed groups, the hepatic protein expression level of phosphorylated 5′ adenosine monophosphate-activated protein kinase (p-AMPK) and plasma adiponectin levels were higher, and the leptin level was lower (p < 0.05). Histological analysis revealed that collagen treatment suppressed hepatic lipid accumulation and reduced the lipid droplet size in the adipose tissue. These effects were increased in a dose-dependent manner. The findings indicated that skate collagen peptide has anti-obesity effects through suppression of fat accumulation and regulation of lipid metabolism.
... Similarly, A. Natalia pulp protein and mineral level is higher than that reported for Caryocar brasilense Camb mesocarp by Leão et al. [32]. However, the mineral content is lower than the 3.8% found in fruit pulp of the palm specie Euterpes oleraceae [33]. ...
The Aphandra natalia palm is a species of monotypic genus Aphandra belonging to the Arecaceae family and is native to South America, mainly in the western part of the Amazon basin in Ecuador, Peru, and Brazil. In this study, we determined the physicochemical characteristics of A. natalia fruit mesocarp, as well as its fatty acid composition, the total polyphenol content (TPC), lipophilic antioxidant compounds and total antioxidant capacity. The fatty acids profile was determined using GC–MS analysis and TPC and antioxidant activity by Folin Ciocalteu’s reagent method and by radical scavenging activity (1,1-diphenyl-2-picrylhydrazyl free radical [DPPH]), respectively regarding their oil. A high value of 57.92% of total lipids was obtained, thus it can be considered as new source of vegetable oil. The oil extracted from A. natalia mesocarp had a high oleic acid content (71.92%), which is a characteristic closer to the composition of olive oil than traditional palm oil. TPC value (83.57 ± 1.84 mg GAE kg⁻¹ of oil) obtained from A. natalia fruit pulp oil is similar to some olive oil varieties. However, its oil presents smaller antioxidant activity than olive oils usually have.
... ere is increasing evidence that polyphenols may protect cell constituents against oxidative damage and, therefore, limit the risk of various degenerative diseases associated with oxidative stress [6]. Studies have repeatedly shown an inverse association between the risk of several chronic human diseases and the consumption of polyphenol-rich diet [7]. e phenolic group of polyphenols can accept an electron to form relatively stable phenoxyl radicals, thereby disrupting chain oxidative reactions in cellular components. ...
Few studies investigated the biological effects of American grape cultivars. We investigated the metabolic response after acute consumption of grape juice or wine from Bordo grapes ( Vitis labrusca ) in a placebo-controlled crossover study with fifteen healthy volunteers. Blood samples were collected 1 hour after the intake of 100 mL of water, juice, or wine to measure TBARS, ABTS, FRAP, glucose, and uric acid levels. To evaluate differences in cellular response, intracellular reactive species production (DCFH-DA) and metabolic mitochondrial viability (MTT) were assessed after exposure of human neuron-like cells (SH-SY5Y) to juice or wine. Glycemia was reduced after juice or wine consumption, whereas blood levels of uric acid were reduced after juice consumption but increased after wine consumption. Juice and wine consumption reduced plasma lipid peroxidation and increased plasma antioxidant capacity (ABTS and FRAP assays). Furthermore, juice inhibited H 2 O 2 -induced intracellular production of reactive species (RS) and increased the viability of SH-SY5Y cells. In contrast, wine (dealcoholized) exhibited a per se effect by inducing the production of RS and reducing cell viability. These results indicate a positive impact of acute consumption of Bordo juice and wine on human oxidative status, whereas only juice had protective effects against oxidative stress-induced cytotoxicity.
... Thus, it was observed that the ability of polyphenols to protect cells against oxidative stress and the reduction of the expression of mRNA and protein levels of pro-inflammatory cytokines when 3T3-L1 cells were compared with TNF-α (Martino et al., 2016). In the same way, it was found that aqueous açaí extract can protect against hepatic steatosis and liver injury and açaí stone extract can attenuate the acute lung inflammation induced by cigarette smoke in a mice experimental model (Guerra et al., 2015;Moura et al., 2012). Xie et al. (2012) reported that velutin (a strong anti-inflammatory flavone) from açaí, has the capacity to reduce TNF-α and IL-6 production, inhibiting the nuclear factor (NF)-κB activation and blocking the degradation effect of NF-κB inhibitor as well as inhibiting mitogen-activated protein kinase p38 and JNK phosphorylation. ...
... Zaobserwowano także wpływ na modulowanie lipogenezy i oksydację kwasów tłuszczowych przez wpływ na zwiększenie wrażliwości wątrobowego receptora 2 adiponektyny (AdipoR2), który aktywuje jądrowy receptor PPAR-alfa. Aktywacja receptora PPAR--alfa była także obserwowana po wprowadzeniu do pożywienia kwasów tłuszczowych wielonienasyconych omega-3 DHA (docosahexaenoic acid) i EPA (eicosapentaenoic acid) [39,40]. ...
... The aç aí (Euterpe oleracea) berry comes from the aç aí palm, a native tree of the Amazon, and this fruit is consumed on a large scale in this region. Besides the folk medicinal use, studies suggest that substances present in aç aí have therapeutic properties such as antiproliferative effects of HT-29 colon cancer cells [1], hypocholesterolemic effect [2], hepatic protection against steatosis [3], antiplasmodium effect [4], neuroprotection effects [5], and antileukemic effects [6]. ...
... Studies have shown that the ingestion of fruits and vegetables rich in polyphenols reduces the risk of several chronic diseases (Boaventura et al., 2013;Crowe et al., 2011;Del Rio et al., 2013;Guerra et al., 2015). Several authors have evaluated the beneficial effects of consuming açaí fruit due to its high antioxidant content (Jensen et al., 2008;Kang et al., 2012;Mertens-Talcott et al., 2008;Schauss et al., 2006). ...
The nutritional properties of juçara fruit are similar to those of açaí fruit, rich in bioactive compounds with antioxidant potential. This cross-over study evaluated the effects of the acute consumption of juçara juice in eleven healthy volunteers. Blood samples were collected before and 1, 2, and 4 h after juice or water (control) intake to measure the ferric reducing antioxidant potential (FRAP), uric acid, reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and lipid hydroperoxides (LH). Repeated measures analysis of variance verified that the treatment increased the FRAP (p = 0.02) and the enzymatic activity of GPx (p = 0.02). In addition, there was a significant treatment–time interaction, and a decrease in LH (p = 0.02) was observed over time after the ingestion of juçara juice. Based on these results, further studies should be carried out to evaluate the clinical effects of juçara juice consumption, particularly regarding its antioxidant potential in humans.
Ethnopharmacological relevance
Diabetic kidney damage (DKD) is one of the most common complications of diabetes, which is known as a chronic inflammatory kidney disease caused by persistent hyperglycemia. White tea was originally used as a folk medicine to treat measles in ancient China. What arouses our interest is that there is a traditional method to treat diabetes with white tea taken from over 30-year-old tree of Camellia sinensis L. However, there are few reports on the renal protection of white tea.
Aim of the study: This present study was designed to study the potential protective effects of white tea (WT) and old tree white tea (OTWT) on high-fat-diet (HFD) combined with streptozotocin (STZ)-induced type 2 diabetic mice to explore the possible mechanism of WT/OTWT against DKD.
Materials and methods
C57BL/6 mice were randomly divided into four groups: NC, T2D, WT (400 mg/kg·b.w, p.o.), OTWT (400 mg/kg·b.w, p.o.). Diabetes was established in all groups except NC group, by six weeks of HFD feeding combined with STZ (50 mg/kg, i.p.) for 3 times, treatments were administered for six weeks and then all the animals were decapitated; kidney tissues and blood samples were collected for the further analysis, including: levels of insulin, lipid metabolism (TG, TC, HDL, LDL, FFA), antioxidative enzymes (catalase (CAT), super oxide dismutase (SOD), glutathione peroxidase (GPx)), blood urea nitrogen (BUN) and creatine, inflammatory cytokines (TNF-α, IL-1β, COX-2, iNOS, MCP-1), advanced glycation end products (AGE), receptor of AGE (RAGE), Nrf2, AMPK, SIRT1, and PGC-1α. H&E, PAS and Masson staining were performed to examine the histopathological alterations of the kidneys.
Results
Our data showed that WT and OTWT reversed the abnormal serum lipids (TG, TC, HDL, LDL, FFA) in T2D mice, upregulated antioxidative enzymes levels (CAT, SOD, GPx) and inhibit the excessive production of proinflammatory mediators (including MCP-1, TNF-α, IL1β, COX-2 and iNOS) by varying degrees, and OTWT was more effective. In histopathology, OTWT could significantly alleviate the accumulation of renal AGE in T2D mice, thereby improving the structural changes of the kidneys, such as glomerular hypertrophy, glomerular basement membrane thickening and kidney FIbrosis.
Conclusions
Both WT and OTWT could alleviate the diabetic changes in T2D mice via hypoglycemic, hypolipidemic, anti-oxidative and anti-inflammatory effects, while OTWT was more evident. OTWT could prominently alleviate the accumulation of AGE in the kidneys of T2D mice, thereby ameliorating the renal oxidative stress and inflammatory damage, which was associated with the activation of SIRT1/AMPK pathway.
This study evaluated the effect of aerobic exercise training (AET) and supplementation with açai on cardiac structure and function in rats submitted to a high-fat diet. Two-month old Fischer male rats were divided into 5 groups: Control (C), High-fat Diet (H), High-fat Diet + Açai (HA), High-fat Diet + AET (HT), High-fat Diet + Açai + AET (HAT). The high-fat diet had 21.8% lard and 1% cholesterol (H and HT), or supplemented with 1% lyophilized açai pulp (HA and HAT). The HT and HAT groups performed AET on a treadmill (5 days/week, 1 h/day, 60% of the maximum running speed) for 8 weeks. Exercise tolerance test were performed, and adiposity index calculated. After euthanasia, the left ventricle (LV) was dissected and processed for histological, single myocyte intracellular calcium ([Ca2+]i) transient and contractility, oxidative stress and gene expression analysis. AET improved running capacity and reduced the adiposity index. Both AET and açai supplementation inhibited the increase in the LV collagen content, the deleterious effects on the [Ca2+]i transient and contractility in cardiomyocytes and the increment in oxidative stress, caused by the consumption of a high-fat diet. Aerobic exercise training and açai supplementation can mitigate damage caused by high-fat diet in cardiac structure and function, though the combination of treatments had no additional effects.
The experiment was to investigate the effect of different dietary lipid levels on the growth performance, nucleic acids, leptin and adiponectin as well as their receptor gene expression in juvenile genetically improved farmed tilapia (GIFT, Oreochromis niloticus). Six groups of the juveniles with 40 days of age in triplicate were fed for 90 days using 6 iso‐nitrogen (34% dietary protein) diets. The 6 diets were control diet contained 0.35% of lipid, without lipid supplementation, and the other diets were added different doses of fish oil to make the different dietary lipid levels of 3.35%, 6.35%, 9.35%, 12.35% and 15.35% based on per kg of dried feed. The samples of whole fish and major tissues/organs were randomly taken at 0 and 90 days for determination, respectively. The main results were as follows: compared with the control diet, the diets with different lipid supplementation improved significantly (p < .05) the specific growth rate (SGR), crude fat, nucleic acids, adiponectin receptors 1 and 2 (AdipoRs 1 & 2) gene expression and serum leptin level in juvenile GIFT tilapia. However, the diets with different lipid supplementation reduced significantly (p < .05) the feed conversion ratio (FCR), hepatosomatic index (HSI), crude protein, leptin receptor (LepR) gene expression and serum adiponectin level. There was no significant effect (p > .05) on the survival rate (SR) in the juveniles fed the diets with different lipid supplementation. In conclusion, the diets with different lipid supplementation could affect significantly the SGR, FCR, HIS, nucleic acids, crude fat and protein, leptin and adiponectin levels and their receptor gene expression of the juveniles. The optimal dietary lipid level was 10.52% for SGR and 10.61% for FCR based on the second‐order polynomial regression analysis between dietary lipid levels against the SGR and FCR of the juveniles, respectively, in the experiment.
The study aimed to investigate the effect of different dietary lipid levels on the growth performance, fatty acids and their relative enzymes, and expression of peroxisome proliferator‐activated receptor α (PPARα), leptin, and adiponectin genes in juvenile genetic improvement farmed tilapia (GIFT, Oreochromis niloticus). Six groups of the juveniles with 40d of age in triplicate were fed for 90 days using six iso‐nitrogen (34 g/100 g dietary protein) diets with different lipid levels: 0.35 (control), 3.35, 6.35, 9.35, 12.35, and 15.35 g/100 g adjusted by adding fish oil. Their samples were respectively analyzed at 0 day and 90 days and the main results were: Compared with the control diet, the diets with lipid supplementation significantly promoted (P < 0.05) the relative weight gain (RWG), daily growth index (DGI), body length gain (BLG), condition factor (CF), protein efficiency ratio (PER), crude fat, polyunsaturated fatty acids (PUFAs), ratio of n‐3 PUFAs and n‐6 PUFAs (n‐3/n‐6), expression of PPARα and leptin (LEP) genes in the juveniles. However, the diets with lipid supplementation significantly decreased (P < 0.05) the saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), activity of lipase and fatty acid synthase (FAS), expression of adiponectin (ADPN) gene and had no significant effect (P > 0.05) on the survival rate (SR) of the juveniles.
We concluded that the greatest effect was found in the diet with 9.35 g/100g of lipid, which is the optimal dietary lipid in the experiment and can be applied in developing the optimal diet for juvenile GIFT tilapia to promote the development of tilapia aquaculture industry.
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The aim of this study was to assess the effect of an addition of sweet cherry fruit or leaves (unexplored until now) to high fat-cholesterol (HFC) diet on selected biochemical parameters and expression of genes involved in fatty acid metabolism in male Wistar rats.
The addition of sweet cherry fruit and leaves to HFC diet resulted in decrease in body gain, improvement of the liver function as well as reduction of oxidative stress and inflammation. Additionally, fruit and leaves had a beneficial impact on lipid metabolism, thereby reducing lipid accumulation in liver and improving lipid profile in the serum. These effects result from the regulation of expression of fatty acid synthesis and oxidation-related genes.
It can be summarized that not only fruit of sweet cherry but also leaves, may have a potential application in the fight against non-communicable diseases, especially obesity and cardiovascular diseases.
The aim was to evaluate the effect of the ethanol extract of bacupari peel (EEB) on biometric measurements, hepatic lipogenesis and progression of non-alcoholic fatty liver disease (NAFLD) in obese Wistar rats. Chemical analysis of the bacupari peel extract identified 7-epiclusianone as the major constituent (140.02 mg/g) followed by morelloflavone (35.86 mg/g). Animals treated with high fat diet plus EEB (BHFD) reduced body mass index (BMI), liver weight and hepatosomatic index in relation to the obese control. The food intake was similar between hyperlipid group (HFD) groups with or without EEB. However, the normal control group (AIN-93 M) presented higher food intake and lower final weight compared to the obese control (HFD). The PPAR-α, CPT-1a and the ADIPOR2 genes expressions, and the concentration of the PPAR-α and the adiponectin protein level increased in the BHFD group in relation to the obese control. The EEB promoted reduction of the SREBP-1c gene expression and the percentage of hepatic fat and the degree of steatosis in relation to HFD. It was concluded that EEB showed a protective effect on NAFLD, as it promoted a reduction in BMI, induced lipid oxidation, reduced lipogenesis and hepatic steatosis. Moreover, our results suggest an interaction that can lead to an agonist activity of the EEB to the PPAR-α receptor.
Açai (Euterpe oleracea Mart.) fruit from the Amazon region in Brazil contains bioactive compounds such as α-tocopherol, anthocyanins (cyanidin 3-glycoside and cyanidin 3-rutinoside), and other flavonoids with antioxidant and anti-inflammatory properties. Moreover, the prebiotic activity of anthocyanins in modulating the composition of gut microbiota has emerged as an additional mechanism by which anthocyanins exert health-promoting effects. Açai consumption may be a nutritional therapeutic strategy for chronic kidney disease (CKD) patients since these patients present with oxidative stress, inflammation, and dysbiosis. However, the ability of açai to modulate these conditions has not been studied in CKD, and this review presents recent information about açai and its possible therapeutic effects in CKD.
Obesity is a serious epidemic pathology whose dangerous visceral fat accumulation initiates nonalcoholic fatty liver disease. This study evaluated the effect of the bioactive compounds of the control and peel extract enriched Ubá mango juices on hepatic steatosis associated with inflammation in obese Wistar rats. Juices were good sources of the β-carotene, presented high concentration of mangiferin and contributed to decrease the liver weight in animals. Total antioxidant capacity was higher in a group fed with control Ubá mango juice and resistin concentration reduced in both test groups intake Ubá mango juices became similar to normal control. In addition, the percentages of fat vesicles and inflammatory infiltrate in the liver was higher to the animals that intake HFD, and both juices reduced these parameters. Therefore, Ubá mango has potential as a functional food and effect to reduce metabolic risk of the hepatic steatosis associated with inflammation.
The aim of this study was to determine the effect of ethanol extract of bacupari peel (EEB) on the adiposity and inflammation modulation in obese Wistar rats. The group treated with high fat diet plus EEB (BHFD) presented weight gain, visceral fat, and lee, and an adiposity index similar to the negative control group (AIN-93M). Also, the BHFD group showed antioxidant and anti-inflammatory effect, increase of peroxisome proliferator activated receptor-γ (PPAR-γ) and Interleukin-10 (IL-10) expression, and decreasing expression of lipoprotein lipase (LPL) and fatty acid synthase (FAS), and reduced the tumor necrosis factor-α (TNF-α), blood levels of glucose, alanine aminotransferase, and adipocyte hypertrophy. The molecular docking showed that morelloflavone and 7-epiclusianone compounds from bacupari extract interacted with PPAR-γ receptor, hydrophobic interaction, indicating an agonist activity of these compounds. Thus, we demonstrated that extract of bacupari presented anti-obesity activities.
A-type procyanidins is rich in litchi pericarp. This study evaluated the prevention and anti-diabetic effect of A-type oligomeric procyanidins (A-OPC). The results showed A-OPC was more effective than B-type oligomeric procyanidins (B-OPC) of lotus seedpod. AMP-activated protein kinase (AMPK) was activated in liver and skeletal muscle. The protein levels of glucokinase (GK), glucose transporter type 2 (GLUT2, in liver), glucose transporter type 4 (GLUT4, in skeletal muscle) and insulin receptor α (INSR) improved significantly with treatment of A-OPC or B-OPC (p < 0.05). Furthermore, the glycolytic key gene expressions of phosphofructokinase (PFK), pyruvate kinase (PK) in liver and skeletal muscle and pyruvate dehydrogenase (PDH) in skeletal muscle were notably up-regulated, while gene expressions, rate-limiting enzymes of gluconeogenesis, of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase) were down-regulated. Both A-OPC and B-OPC improved glucose homeostasis by inhibiting the glucose production in liver, regulating the expression of proteins involved in glucose transport system and increasing glycolysis.
The anti-lipidaemic and anti-inflammatory effects of açai polyphenols in 3T3-L1 mouse adipocytes were investigated. Pre-adipocytes were differentiated with and without açai-polyphenols at concentrations of 2.5, 5 and 10 µg gallic acid equivalents (GAE)/mL. Results showed that açai polyphenols reduce the accumulation of intracellular lipids in differentiated adipocytes in a dose-dependent manner and downregulated PPARγ2. The gene-expression of adipogenic transcription factors C/ebpα, C/ebpβ, Klf5 and Srebp1c was decreased. This was accompanied by a reduction of adipogenic genes, including aP2, LPL, FATP1 and FAS, leptin and total PAI and an increase of adiponectin. Additionally, açai polyphenols protected cells against the production of ROS and decreased the expression of mRNA and protein levels of pro-inflammatory cytokines when 3T3-L1 cells were challenged with TNF-α. Thus, these results indicate that açai polyphenols may be useful in the prevention of adipogenesis, oxidative stress and inflammation.
The effects of esculetin on hepatosteatosis and insulin resistance in high-fat diet (HFD)-induced obese mice were investigated. Esculetin (0.02%, w/w) provided to mice fed a HFD (40% kcal from fat) for 12 weeks reduced body weight gain, visceral adiposity, hepatosteatosis, hyperlipidemia and hyperglycemia, whereas it increased plasma adiponectin level and the protein and mRNA expression of hepatic AdipoR2, which led to the activation of AMPK. The protein and mRNA expression of hepatic PPARα were up-regulated by esculetin and those of SREBP-1c were down-regulated. Esculetin elevated expression of hepatic fatty acid oxidation genes (PGC-1α, PPARα, Acsl1 and CPT), while suppressing expression of fatty acid synthesis gene. Anti-insulin resistant effects of esculetin were mediated by increased hepatic GLUT2 and glucokinase mRNA levels and decreased glucose-6-phosphatase mRNA level. These findings suggest that esculetin supplementation has beneficial effects on hepatosteatosis and insulin resistance in HFD-induced obese mice, partly via activation of the AdiopR2–AMPK pathway.
Adiponectin is an adipose tissue-secreted adipokine with beneficial effects on the cardiovascular system. In this study, we evaluated a potential role for adiponectin in the protective effects of anthocyanin on diabetes-related endothelial dysfunction. We treated db/db mice on a normal diet with anthocyanin C3G (2 g/kg diet) for 8 weeks. Endothelium-dependent and independent relaxation of the aorta was then evaluated. Adiponectin expression and secretion were also measured. C3G treatment restores endothelium- dependent relaxation of the aorta in db/db mice, whereas diabetic mice treated with an anti-adiponectin antibody do not respond. C3G treatment induces adiponectin expression and secretion in cultured 3T3 adipocytes through transcription factor forkhead box O1 (Foxo1). Silencing Foxo1 expression prevented C3G-stimulated induction of adiponectin expression. In contrast, overexpression of Foxo1-ADA promoted adiponectin expression in adipocytes. C3G activates Foxo1 by increasing its deacetylation via silent mating type information regulation 2 homolog 1 (Sirt1). Furthermore, purified anthocyanin supplementation significantly improved flow-mediated dilation (FMD) and increased serum adiponectin concentrations in patients with type 2 diabetes. Changes in adiponectin concentrations positively correlated with FMD in the anthocyanin group. Mechanistically, adiponectin activates cAMP/PKA/eNOS signaling pathways in HAECs, increasing endothelial nitric oxide (NO) bioavailability. These results demonstrate that adipocyte-derived adiponectin is required for anthocyanin C3G-mediated improvement of endothelial function in diabetes.
Nonalcoholic fatty liver disease (NAFLD), defined by excessive lipid accumulation in the liver, is the hepatic manifestation of insulin resistance and the metabolic syndrome. Due to the epidemics of obesity, NAFLD is rapidly becoming the leading cause of altered liver enzymes in Western countries. NAFLD encompasses a wide spectrum of liver disease ranging from simple uncomplicated steatosis, to steatohepatitis, cirrhosis, and hepatocellular carcinoma. Diet may affect the development of NAFLD either by increasing risk or by providing protective factors. Therefore, it is important to investigate the role of foods and/or food bioactives on the metabolic processes involved in steatohepatitis for preventive strategies. It has been reported that anthocyanins (ACNs) decrease hepatic lipid accumulation and may counteract oxidative stress and hepatic inflammation, but their impact on NAFLD has yet to be fully determined. ACNs are water-soluble bioactive compounds of the polyphenol class present in many vegetable products. Here, we summarize the evidence evaluating the mechanisms of action of ACNs on hepatic lipid metabolism in different experimental setting: in vitro, in vivo, and in human trials. Finally, a working model depicting the possible mechanisms underpinning the beneficial effects of ACNs in NAFLD is proposed, based on the available literature.
The peel of the native Brazilian fruit jaboticaba is rich in anthocyanins, which are known for their anti-obesity effects in animal models. The aim of the present study was to evaluate the effects of freeze-dried jaboticaba peel powder (FDJPP) on a number of metabolic parameters in a model of diet-induced obesity. Mice (n 8 per group) were initially fed on a high-fat diet (HFD, 35 % w/w) for 4 weeks and then switched to a HFD supplemented with FDJPP (1, 2 or 4 % w/w) for an additional 6 weeks. Energy intake, weight loss, glucose tolerance, insulin resistance and lipid profile were determined, and the results were evaluated using ANOVA and Tukey's tests. The FDJPP exerted no protective effect on HFD-induced weight gain, hyperleptinaemia and glucose intolerance. However, the supplementation was effective to reduce insulin resistance, as evidenced in the insulin tolerance test, and subsequently confirmed by improved signal transduction through the insulin receptor/insulin receptor substrate-1/Akt/forkhead box protein pathway and by the attenuation of HFD-induced inflammation in the liver, verified by lower expressions of IL-1β and IL-6 and decreased phosphorylated IκB-α protein levels in all jaboticaba-treated mice. These results suggest that FDJPP may exert a protective role against obesity-associated insulin resistance.
The polyphenolic composition of Euterpe oleracea Mart. (Aai palm) fruit was investigated by HPLC-DAD-UV-Vis and HPLC-MS. Aai palm is widely diffused and cultivated in Amazon regions and especially in the Par state (Brazil), because the pulp of the fruit is largely consumed as food. This study confirms the presence of cyanidin 3-O-glucoside and cyanidin 3-O-rutinoside as major anthocyanic compounds. Moreover, four main compounds were also identified for the first time, i.e. homoorientin, orientin, taxifolin deoxyhexose, and isovitexin. Traces of a methyl-derivative of homoorientin were also detected. The amount of total anthocyanins was 0.5 mg g–1 of the dried pulp weight and the amount of the other flavonoids was 3.5 mg g–1 of the dried pulp weight. No other reports on the presence of non-anthocyanic flavonoids in Euterpe oleracea Mart. have been found so far.
Açai (Euterpe oleracea Mart.) has recently emerged as a promising source of natural antioxidants. Because increased oxidative stress and impaired antioxidant defense mechanisms are important factors in the development of diabetic complications and many health claims have been reported for açai, the present study was undertaken to evaluate the possible protective effects of açai on the production of reactive oxygen species by neutrophils and on the liver antioxidant defense system in control and streptozotocin-induced diabetic rats. Diet supplementation with 2% açai was found to increase mRNA levels for gamma-glutamylcysteine synthetase and glutathione peroxidase in liver tissue and to decrease reactive oxygen species production by neutrophils. Compared to control animals, diabetic rats exhibited lower levels of mRNA coding for Zn-superoxide dismutase, glutathione peroxidase and gamma-glutamylcysteine synthetase and higher levels of reactive oxygen species production by neutrophils, thiobarbituric acid-reactive substances and carbonyl proteins in hepatic tissues. Although açai supplementation was not effective in restore gene expression of antioxidant enzymes in diabetic rats, it showed a protective effect, decreasing thiobarbituric acid-reactive substances levels and increasing reduced glutathione content in the liver. These findings suggest that açai can modulate reactive oxygen species production by neutrophils and that it has a significant favorable effect on the liver antioxidant defense system under fisiological conditions of oxidative stress and partially revert deleterious effects of diabetes in the liver.
The worldwide prevalence of obesity and related metabolic disorders is rising rapidly, increasing the burden on our healthcare system. Obesity is often accompanied by excess fat storage in tissues other than adipose tissue, including liver and skeletal muscle, which may lead to local insulin resistance and may stimulate inflammation, as in steatohepatitis. In addition, obesity changes the morphology and composition of adipose tissue, leading to changes in protein production and secretion. Some of these secreted proteins, including several proinflammatory mediators, may be produced by macrophages resident in the adipose tissue. The changes in inflammatory status of adipose tissue and liver with obesity feed a growing recognition that obesity represents a state of chronic low-level inflammation. Various molecular mechanisms have been implicated in obesity-induced inflammation, some of which are modulated by the peroxisome proliferator-activated receptors (PPARs). PPARs are ligand-activated transcription factors involved in the regulation of numerous biological processes, including lipid and glucose metabolism, and overall energy homeostasis. Importantly, PPARs also modulate the inflammatory response, which makes them an interesting therapeutic target to mitigate obesity-induced inflammation and its consequences. This review will address the role of PPARs in obesity-induced inflammation specifically in adipose tissue, liver, and the vascular wall.
The purpose of this study was to evaluate the effect of açai fruit pulp on risk factors for metabolic disorders in overweight subjects. The açaí palm (Euterpe oleracea Mart.), which is native to South America, produces a small, black-purple fruit which is edible. The fruit has recently become popular as a functional food due to its antioxidant potential. Although several studies have been conducted in vitro and with animals, little is known about the potential health benefits in humans aside from an increase in plasma anti-oxidant capacity. Metabolic syndrome is a condition which is defined by a cluster of risk factors for cardiovascular disease and/or type-2 diabetes. Preliminary studies indicate that a reduction in reactive oxygen species can assist in the normalization of the metabolic pathways involved in this syndrome.
This was an open label pilot study conducted with 10 overweight adults (BMI ≥ 25 kg/m² and ≤ 30 kg/m²) who took 100 g açai pulp twice daily for 1 month. The study endpoints included levels of fasting plasma glucose, insulin, cholesterol, triglycerides, exhaled (breath) nitric oxide metabolites (eNO) and plasma levels of high sensitivity C-reactive protein (hs-CRP). The response of blood glucose, blood pressure and eNO to a standardized meal was determined at baseline and following the 30 day treatment.
Compared to baseline, there were reductions in fasting glucose and insulin levels following the 30 day treatment (both p < 0.02). There was also a reduction in total cholesterol (p = 0.03), as well as borderline significant reductions in LDL-cholesterol and the ratio of total cholesterol to HDL-cholesterol (both p = 0.051). Compared to baseline, treatment with açai ameliorated the post-prandial increase in plasma glucose following the standardized meal, measured as the area under the curve (p = 0.047). There was no effect on blood pressure, hs-CRP or eNO.
In this uncontrolled pilot study, consumption of açai fruit pulp reduced levels of selected markers of metabolic disease risk in overweight adults, indicating that further studies are warranted.
Açaí fruit pulp has received much attention because of its high antioxidant capacity and potential anti-inflammatory effects. In this study, athero-protective effects of açaí juice were investigated in apolipoprotein E deficient (apoE(-/-)) mice.
ApoE(-/-) mice were fed AIN-93G diet (CD) or CD formulated to contain 5% freeze-dried açaí juice powder (AJ) for 20 weeks. The mean lesion areas in the aorta for apoE(-/-) mice fed AJ were 58% less (P<0.001) compared to that for CD fed mice. HDL-cholesterol was higher in AJ fed mice. Biomarkers of lipid peroxidation, including F(2)-isoprostanes and isomers of hydroxyoctadecadienoic acids and hydroxyeicosatetraenoic acids were significantly lower in serum and in liver of AJ fed mice. Expression of the two antioxidant enzyme genes, Gpx3 and Gsr, were significantly up-regulated in the aorta from AJ fed mice. The activity of GPX, GSR and PON1 increased in serum and/or liver of mice fed AJ. In the second experiment, ApoE(-/-) mice were fed CD or AJ for 5 weeks. Serum levels, gene expression and protein levels of the two proinflammatory cytokines TNF-α and IL-6 in the resident macrophages with or without LPS stimulation were lower in mice fed AJ. SEAP reporter assay determined that AJ reduced NF-κB activation.
Reducing lipid peroxidation through boosting antioxidant enzymes and inhibiting pro-inflammatory cytokine production are proposed as major underlying mechanisms for the athero-protective effects of the açaí juice tested in these experimental in vivo models.
Fatty acid translocase CD36 (FAT/CD36) mediates uptake and intracellular transport of long-chain fatty acids in diverse cell types. While the pathogenic role of FAT/CD36 in hepatic steatosis in rodents is well-defined, little is known about its significance in human liver diseases.
To examine the expression of FAT/CD36 and its cellular and subcellular distribution within the liver of patients with non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis C virus (HCV) infection.
34 patients with non-alcoholic steatosis (NAS), 30 with non-alcoholic steatohepatitis (NASH), 66 with HCV genotype 1 (HCV G1) and 32 with non-diseased liver (NL).
Real-time PCR and western blot analysis were used to assess hepatic FAT/CD36 expression. Computational image analysis of immunostained liver biopsy sections was performed to determine subcellular distribution and FAT/CD36 expression index.
Compared with NL, hepatic mRNA and protein levels of FAT/CD36 were significantly higher in patients with NAS (median fold increase 0.84 (range 0.15-1.61) and 0.66 (range 0.33-1.06), respectively); NASH (0.91 (0.22-1.81) and 0.81 (0.38-0.92), respectively); HCV G1 without steatosis (0.30 (0.17-1.59) and 0.33 (0.29-0.52), respectively); and HCV G1 with steatosis (0.85 (0.15-1.98) and 0.87 (0.52-1.26), respectively). In contrast to NL, FAT/CD36 was predominantly located at the plasma membrane of hepatocytes in patients with NAFLD and HCV G1 with steatosis. A significant correlation was observed between hepatic FAT/CD36 expression index and plasma insulin levels, insulin resistance (HOMA-IR) and histological grade of steatosis in patients with NASH (r=0.663, r=0.735 and r=0.711, respectively) and those with HCV G1 with steatosis (r=0.723, r=0.769 and r=0.648, respectively).
Hepatic FAT/CD36 upregulation is significantly associated with insulin resistance, hyperinsulinaemia and increased steatosis in patients with NASH and HCV G1 with fatty liver. Translocation of this fatty acid transporter to the plasma membrane of hepatocytes may contribute to liver fat accumulation in patients with NAFLD and HCV.
For sixteen years, the American institute of Nutrition Rodent Diets, AIN-76 and AIN-76A, have been used extensively around the world. Because of numerous nutritional and technical problems encountered with the diet during this period, it was revised. Two new formulations were derived: AIN-93G for growth, pregnancy and lactation, and AIN-93M for adult maintenance. Some major differences in the new formulation of AIN-93G compared with AIN-76A are as follows: 7 g soybean oil/100 g diet was substituted for 5 g corn oil/ 100 g diet to increase the amount of linolenic acid; cornstarch was substituted for sucrose; the amount of phosphorus was reduced to help eliminate the problem of kidney calcification in female rats; L-cystine was substituted for DL-methionine as the amino acid supplement for casein, known to be deficient in the sulfur amino acids; manganese concentration was lowered to one-fifth the amount in the old diet; the amounts of vitamin E, vitamin K and vitamin B-12 were increased; and molybdenum, silicon, fluoride, nickel, boron, lithium and vanadium were added to the mineral mix. For the AIN-93M maintenance diet, the amount of fat was lowered to 40 g/kg diet from 70 g/kg diet, and the amount of casein to 140 g/kg from 200 g/kg in the AIN-93G diet. Because of a better balance of essential nutrients, the AIN-93 diets may prove to be a better choice than AIN-76A for long-term as well as short-term studies with laboratory rodents.
Following on from impressive economic development and urbanization, China is currently experiencing a high prevalence of metabolic syndrome. Patients with metabolic syndrome suffer from the "The Deadly Quartet" of hyperglycemia, hypertriglyceridemia, hypertension, and central (or upper body) obesity. Current treatment strategies directed towards metabolic syndrome tend to be limited to just one of these four conditions, so developing novel drugs to target multiple metabolic abnormalities could be preferable to current approaches. New insights suggest benefits of natural agents as treatments for metabolic syndrome. Herein, we review the evidence for using nine such agents developed on the basis of traditional medicine or herbal preparations.
Hepatic steatosis is common in non-insulin-dependent diabetes and can be associated with fibrosis and cirrhosis in a subset of individuals. Increased rates of fatty acid synthesis have been reported in livers from rodent models of diabetes and may contribute to the development of steatosis. Sterol regulatory element-binding proteins (SREBPs) are a family of regulated transcription factors that stimulate lipid synthesis in liver. In the current studies, we measured the content of SREBPs in livers from two mouse models of diabetes, obese ob/ob mice and transgenic aP2-SREBP-1c436 (aP2-SREBP-1c) mice that overexpress nuclear SREBP-1c only in adipose tissue. The aP2-SREBP-1c mice exhibit a syndrome that resembles congenital generalized lipodystrophy in humans. Both lines of mice develop hyperinsulinemia, hyperglycemia, and hepatic steatosis. Nuclear SREBP-1c protein levels were significantly elevated in livers from ob/ob and aP2-SREBP-1c mice compared with wild-type mice. Increased nuclear SREBP-1c protein was associated with elevated mRNA levels for known SREBP target genes involved in fatty acid biosynthesis, which led to significantly higher rates of hepatic fatty acid synthesis in vivo. These studies suggest that increased levels of nuclear SREBP-1c contribute to the elevated rates of hepatic fatty acid synthesis that leads to steatosis in diabetic mice.
Insulin sensitivity (euglycemic clamp, insulin infusion rate: 40 mU. m(-2). min(-1)) was studied in 30 subjects with biopsy-proven nonalcoholic fatty liver disease (NAFLD), normal glucose tolerance, and a BMI <30 kg/m(2). Of those 30 subjects, 9 had pure fatty liver and 21 had evidence of steatohepatitis. In addition, 10 patients with type 2 diabetes under good metabolic control and 10 healthy subjects were studied. Most NAFLD patients had central fat accumulation, increased triglycerides and uric acid, and low HDL cholesterol, irrespective of BMI. Glucose disposal during the clamp was reduced by nearly 50% in NAFLD patients, as well as in patients with normal body weight, to an extent similar to that of the type 2 diabetic patients. Basal free fatty acids were increased, whereas insulin-mediated suppression of lipolysis was less effective (-69% in NAFLD vs. -84% in control subjects; P = 0.003). Postabsorptive hepatic glucose production (HGP), measured by [6,6-(2)H(2)]glucose, was normal. In response to insulin infusion, HGP decreased by only 63% of basal in NAFLD vs. 84% in control subjects (P = 0.002). Compared with type 2 diabetic patients, NAFLD patients were characterized by lower basal HGP, but with similarly reduced insulin-mediated suppression of HGP. There was laboratory evidence of iron overload in many NAFLD patients, but clinical, histological, and biochemical data (including insulin sensitivity) were not correlated with iron status. Four subjects were heterozygous for mutation His63Asp of the HFE gene of familiar hemochromatosis. We concluded that NAFLD, in the presence of normoglycemia and normal or moderately increased body weight, is characterized by clinical and laboratory data similar to those found in diabetes and obesity. NAFLD may be considered an additional feature of the metabolic syndrome, with specific hepatic insulin resistance.
Adiponectin, the most abundant adipose-specific protein, has been found to be negatively associated with degree of adiposity and positively associated with insulin sensitivity in Pima Indians and other populations. Moreover, adiponectin administration to rodents has been shown to increase insulin-induced tyrosine phosphorylation of the insulin receptor (IR) and also increase whole-body insulin sensitivity. To further characterize the relationship between plasma adiponectin concentration and insulin sensitivity in humans, we examined 1) the cross-sectional association between plasma adiponectin concentration and skeletal muscle IR tyrosine phosphorylation and 2) the prospective effect of plasma adiponectin concentration at baseline on change in insulin sensitivity. Fasting plasma adiponectin concentration, body composition (hydrodensitometry or dual energy X-ray absorptiometry), insulin sensitivity (insulin-stimulated glucose disposal, hyperinsulinemic clamp), and glucose tolerance (75-g oral glucose tolerance test) were measured in 55 Pima Indians (47 men and 8 women, aged 31 +/- 8 years, body fat 29 +/- 8% [mean +/- SD]; 50 with normal glucose tolerance, 3 with impaired glucose tolerance, and 2 with diabetes). Group 1 (19 subjects) underwent skeletal muscle biopsies for the measurement of basal and insulin-stimulated tyrosine phosphorylation of the IR (stimulated by 100 nmol/l insulin). The fold increase after insulin stimulation was calculated as the ratio between maximal and basal phosphorylation. Group 2 (38 subjects) had follow-up measurements of insulin-stimulated glucose disposal. Cross-sectionally, plasma adiponectin concentration was positively associated with insulin-stimulated glucose disposal (r = 0.58, P < 0.0001) and negatively associated with percent body fat (r = -0.62, P < 0.0001) in the whole group. In group 1 plasma adiponectin was negatively associated with the basal (r = -0.65, P = 0.003) and positively associated with the fold increase in IR tyrosine phosphorylation (r = 0.69, P = 0.001) before and after the adjustment for percent body fat (r = -0.58, P = 0.01 and r = 0.54, P = 0.02, respectively). Longitudinally, after adjustment for age, sex, and percent body fat, low plasma adiponectin concentration at baseline was associated with a decrease in insulin sensitivity (P = 0.04). In conclusion, our cross-sectional data suggest a role of physiological concentration of fasting plasma adiponectin in the regulation of skeletal muscle IR tyrosine phosphorylation. Prospectively, low plasma adiponectin concentration at baseline precedes a decrease in insulin sensitivity. Our data indicate that adiponectin plays an important role in regulation of insulin sensitivity in humans.
Adiponectin has recently been shown to be a promising candidate for the treatment of obesity-associated metabolic syndromes. Replenishment of recombinant adiponectin in mice can decrease hyperglycemia, reverse insulin resistance, and cause sustained weight loss without affecting food intake. Here we report its potential roles in alcoholic and nonalcoholic fatty liver diseases in mice. Circulating concentrations of adiponectin decreased significantly following chronic consumption of high-fat ethanol-containing food. Delivery of recombinant adiponectin into these mice dramatically alleviated hepatomegaly and steatosis (fatty liver) and also significantly attenuated inflammation and the elevated levels of serum alanine aminotransferase. These therapeutic effects resulted partly from the ability of adiponectin to increase carnitine palmitoyltransferase I activity and enhance hepatic fatty acid oxidation, while it decreased the activities of two key enzymes involved in fatty acid synthesis, including acetyl-CoA carboxylase and fatty acid synthase. Furthermore, adiponectin treatment could suppress the hepatic production of TNF-alpha and plasma concentrations of this proinflammatory cytokine. Adiponectin was also effective in ameliorating hepatomegaly, steatosis, and alanine aminotransferase abnormality associated with nonalcoholic obese, ob/ob mice. These results demonstrate a novel mechanism of adiponectin action and suggest a potential clinical application of adiponectin and its agonists in the treatment of liver diseases.
Epidemiological studies have consistently shown that regular consumption of fruits and vegetables is strongly associated with reduced risk of developing chronic diseases, such as cancer and cardiovascular disease. It is now widely believed that the actions of the antioxidant nutrients alone do not explain the observed health benefits of diets rich in fruits and vegetables, because taken alone, the individual antioxidants studied in clinical trials do not appear to have consistent preventive effects. Work performed by our group and others has shown that fruits and vegetable phytochemical extracts exhibit strong antioxidant and anti proliferative activities and that the major part of total antioxidant activity is from the combination of phytochemicals. We proposed that the additive and synergistic effects of phytochemicals in fruits and vegetables are responsible for these potent antioxidant and anticancer activities and that the benefit of a diet rich in fruits and vegetables is attributed to the complex mixture of phytochemicals present in whole foods. This explains why no single antioxidant can replace the combination of natural phytochemicals in fruits and vegetables to achieve the health benefits. The evidence suggests that antioxidants or bioactive compounds are best acquired through whole-food consumption, not from expensive dietary supplements. We believe that a recommendation that consumers eat 5 to 10 servings of a wide variety of fruits and vegetables daily is an appropriate strategy for significantly reducing the risk of chronic diseases and to meet their nutrient requirements for optimum health.
Estimating flavonoid intake is a first step toward documenting the protective effects of flavonoids against risk of chronic diseases. Although flavonoids are important dietary sources of antioxidants, insufficient data on the comprehensive food composition of flavonoids have delayed the assessment of dietary intake in a population. We aimed to estimate the dietary flavonoid intake in U.S. adults and its sociodemographic subgroups and to document major dietary sources of flavonoids. We expanded the recently released USDA Flavonoid Database to increase its correspondence with the 24-h dietary recall (DR) of the NHANES 1999–2002. We systematically assigned a particular food code to all foods that were prepared or processed similarly. This expanded database included 87% of fruits and fruit juices, 86% of vegetables, 75% of legumes, and, overall, 45% of all foods reported by the 24-h DR of the NHANES 1999–2002. Estimated mean daily total flavonoid intake, 189.7 mg/d, was mainly from flavan-3-ols (83.5%), followed by flavanones (7.6%), flavonols (6.8%), anthocyanidins (1.6%), flavones (0.8%), and isoflavones (0.6%). The flavonoid density of diets increased with age (P < 0.001) and income (P < 0.05). It was higher in women (P < 0.001), Caucasians (P < 0.001), and vitamin supplement users (P < 0.001) and lower in adults with high levels of nonleisure time physical activity (P < 0.01) compared with their counterparts. The greatest daily mean intake of flavonoids was from the following foods: tea (157 mg), citrus fruit juices (8 mg), wine (4 mg), and citrus fruits (3 mg). The proposed relation between flavonoid intake and the prevention of chronic diseases needs further investigation using the estimates introduced in this study.
Adiponectin (also known as 30-kDa adipocyte complement-related protein; Acrp30) is a hormone secreted by adipocytes that acts as an antidiabetic and anti-atherogenic adipokine. Levels of adiponectin in the blood are decreased under conditions of obesity, insulin resistance and type 2 diabetes. Administration of adiponectin causes glucose-lowering effects and ameliorates insulin resistance in mice. Conversely, adiponectin-deficient mice exhibit insulin resistance and diabetes. This insulin-sensitizing effect of adiponectin seems to be mediated by an increase in fatty-acid oxidation through activation of AMP kinase and PPAR-alpha. Here we report the cloning of complementary DNAs encoding adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2) by expression cloning. AdipoR1 is abundantly expressed in skeletal muscle, whereas AdipoR2 is predominantly expressed in the liver. These two adiponectin receptors are predicted to contain seven transmembrane domains, but to be structurally and functionally distinct from G-protein-coupled receptors. Expression of AdipoR1/R2 or suppression of AdipoR1/R2 expression by small-interfering RNA supports our conclusion that they serve as receptors for globular and full-length adiponectin, and that they mediate increased AMP kinase and PPAR-alpha ligand activities, as well as fatty-acid oxidation and glucose uptake by adiponectin.
Adipose differentiation is accompanied by changes in cellular morphology, a dramatic accumulation of intracellular lipid and
activation of a specific program of gene expression. Using an mRNA differential display technique, we have isolated a novel
adipose cDNA, termed adipoQ. The adipoQ cDNA encodes a polypeptide of 247 amino acids with a secretory signal sequence at
the amino terminus, a collagenous region (Gly-X-Y repeats), and a globular domain. The globular domain of adipoQ shares significant
homology with subunits of complement factor C1q, collagen α1(X), and the brain-specific factor cerebellin. The expression
of adipoQ is highly specific to adipose tissue in both mouse and rat. Expression of adipoQ is observed exclusively in mature
fat cells as the stromal-vascular fraction of fat tissue does not contain adipoQ mRNA. In cultured 3T3-F442A and 3T3-L1 preadipocytes,
hormone-induced differentiation dramatically increases the level of expression for adipoQ. Furthermore, the expression of
adipoQ mRNA is significantly reduced in the adipose tissues from obese mice and humans. Whereas the biological function of
this polypeptide is presently unknown, the tissue-specific expression of a putative secreted protein suggests that this factor
may function as a novel signaling molecule for adipose tissue.
We attempted to determine whether blueberry anthocyanins (BA) would be protective against cyclophosphamide (CTX)-induced liver injury in SD rats. CTX was injected intraperitoneally into rats to induce liver toxicity. The rats were randomly divided into four groups: a control group, a CTX group, and two groups received BA at doses of 20 and 80 mg/kg/day for 7 days (i.g.), both before and after they were administered CTX. Liver histopathology, serum liver enzymatic activities, cytokines and apoptotic parameters were evaluated. The rats that were injected with CTX incurred liver injury, evidenced by histological changes and elevated serum enzymes activities; CTX led to elevated proinflammatory cytokines, and reduced anti-inflammatory cytokine; also induced apoptosis, indicated by increased Bax and TLR4, and decreased Bcl-2 expression in western blot assay, which was further confirmed by immunohistochemistry assay with anti-Bax antibody. BA had a protective effect against CTX-induced liver damage in rats.
Anthocyanins are naturally occurring compounds widespread in plant-derived foodstuffs and therefore abundant in human diet. There are evidences regarding the positive association of their intake with healthy biological effects displayed in vivo. This review aims to highlight some aspects regarding anthocyanins bioavailability; these include a short introductory part of anthocyanin chemistry, stability, occurrence and intake.
This first part is followed by a more detailed one concerning the main topic of the review that includes the bioavailability and metabolism of anthocyanins. Special attention is given to the contribution of the gastric mucosa to anthocyanin absorption as the result of the high content of intact anthocyanins (20–25%) detected is plasma few minutes after intake. The contribution of intestinal tissue and the microbiota impact in anthocyanin absorption and bioactivity is also highlighted. Despite the biological activities that have been associated with these compounds, anthocyanins appear to be rapidly absorbed and eliminated, reaching only low maximal concentrations in plasma and urine. Some possible critical factors that may contribute to this paradox were also explored including the ability of a compound to cross membranes, the effect of pH, digestive enzymes, biliary acids and microbiota, the lack of sensitivity of the analytical method, the possible ingestion of pigments (anthocyanin derivatives, especially in the case of red wine) and the influence of the food matrix.
Generally, the bioavailability of anthocyanins is presumed but whether the effect is due to the native compounds or other forms, which mechanism are involved or which factors have crucial impact on bioavailability still remain underexplored.
Fat accumulation in the liver increases the risk of developing progressive liver injury. It can induce all the symptoms of metabolic syndrome, which is associated with many additional health problems, including increased risk of obesity, hypertension, insulin resistance, and non-alcoholic fatty liver disease (NAFLD). Therefore, prevention and treatment of fat accumulation in the liver are relevant to health promotion. Mulberry leaf polyphenol extracts (MLPE) have been known to modulate serum fasting glucose, lipid and antiatherosclerosis. However, the effect of MLPE on regulating hepatic lipid metabolism is unclear. This study evaluated the effects and mechanisms of MLPE in reducing hepatic lipid accumulation in cell culture. We found MLPE could regulate hepatic lipid accumulation. Further, numerous lipogenic enzymes, such as FAS (fatty acid synthetase), ACC (acetyl-CoA carboxylase), HMGCR (HMG-CoA reductase) and associated-lipogenic transcriptional factors (SREBP1 and SREBP2) were suppressed by MLPE. Our results show MLPE is able to reduce hepatic lipid accumulation through activation of the AMPK (AMP-activating protein kinase) signaling pathway. It may have potential therapeutic implications for human NFALD.
Fatty liver disease that develops in the absence of alcohol abuse is recognized increasingly as a major health burden. This report summarizes the presentations and discussions at a Single Topic Conference held September 20-22, 2002, and sponsored by the American Association for the Study of Liver Diseases. The conference focused on fatty liver disorders. Estimates based on imaging and autopsy studies suggest that about 20% to 30% of adults in the United States and other Western countries have excess fat accumulation in the liver. About 10% of these individuals, or fully 2% to 3% of adults, are estimated to meet current diagnostic criteria for nonalcoholic steatohepatitis (NASH). Sustained liver injury leads to progressive fibrosis and cirrhosis in a fraction, possibly up to one third, of those with NASH, and NASH may be a cause of cryptogenic cirrhosis. NASH is now a significant health issue for obese children as well, leading to cirrhosis in some. The diagnostic criteria for NASH continue to evolve and rely on the histologic findings of steatosis, hepatocellular injury (ballooning, Mallory bodies), and the pattern of fibrosis. Generally recognized indications for biopsy include establishing the diagnosis and staging of the injury, but strict guidelines do not exist. Liver enzymes are insensitive and cannot be used reliably to confirm the diagnosis or stage the extent of fibrosis. Older age, obesity, and diabetes are predictive of fibrosis. The pathogenesis of NASH is multifactorial. Insulin resistance may be an important factor in the accumulation of hepatocellular fat, whereas excess intracellular fatty acids, oxidant stress, adenosine triphosphate (ATP) depletion, and mitochondrial dysfunction may be important causes of hepatocellular injury in the steatotic liver. Efforts are underway to refine the role of insulin resistance in NASH and determine whether improving insulin sensitivity pharmacologically is an effective treatment. An altered lifestyle may be a more effective means of improving insulin sensitivity. The research agenda for the future includes establishing the role of insulin resistance and abnormal lipoprotein metabolism in NASH, determining the pathogenesis of cellular injury, defining predisposing genetic abnormalities, identifying better noninvasive predictors of disease, and defining effective therapy.
Previous studies have demonstrated that the ingestion of açaí pulp can improve serum lipid profile in various animal models; therefore, we hypothesized that açaí pulp (Euterpe oleracea Mart.) may modulate the expression of the genes involved in cholesterol homeostasis in the liver and increase fecal excretion, thus reducing serum cholesterol. To test this hypothesis, we analyzed the expression of 7α-hydroxylase and ATP-binding cassette, subfamily G transporters (ABCG5 and ABCG8), which are genes involved with the secretion of cholesterol in the rat. We also evaluated the expression of sterol regulatory element-binding protein 2, 3-hydroxy-3-methylglutaryl CoA reductase, low-density lipoprotein receptor (LDL-R), and apolipoprotein B100, which are involved in cholesterol biosynthesis. Female Fischer rats were divided into 4 groups: the C group, which was fed a standard AIN-93 M diet; the CA group, which was fed a standard diet supplemented with 2% açaí pulp; the H group, which was fed a hypercholesterolemic diet (25% soy oil and 1% cholesterol); and the HA group, which was fed a hypercholesterolemic diet supplemented with 2% açaí pulp. At the end of the experimental period, the rats were euthanized, and their blood and livers were collected. The HA group exhibited a significant decrease in serum total cholesterol, low-density lipoprotein cholesterol, and atherogenic index and also had increased high-density lipoprotein cholesterol and cholesterol excretion in feces compared with the H group. In addition, the expression of the LDL-R, ABCG5, and ABCG8 genes was significantly increased by the presence of açaí pulp. These results suggest that açaí pulp promotes a hypocholesterolemic effect in a rat model of dietary-induced hypercholesterolemia through an increase in the expression of ATP-binding cassette, subfamily G transporters, and LDL-R genes.
To investigate underlying mechanism of targets of cyanidin, a flavonoid, exhibits potent anti-atherogenic activities in vitro and in vivo, a natural chemical library identified potent agonistic activity between cyanidin and peroxisome proliferator-activated receptors (PPAR) was performed. Cyanidin induced transactivation activity in all three PPAR subtypes in a reporter gene assay and time-resolved fluorescence energy transfer analyses. Cyanidin also bound directly to all three subtypes, as assessed by surface plasmon resonance experiments, and showed the greatest affinity to PPARα. These effects were confirmed by measuring the expression of unique genes of each PPAR subtype. Cyanidin significantly reduced cellular lipid concentrations in lipid-loaded steatotic hepatocytes. In addition, transcriptome profiling in lipid-loaded primary hepatocytes revealed that the net effects of stimulation with cyanidin on lipid metabolic pathways were similar to those elicited by hypolipidemic drugs. Cyanidin likely acts as a physiological PPARα agonist and potentially for PPARβ/δ and γ, and reducing hepatic lipid concentrations by rewiring the expression of genes involved in lipid metabolic pathways.
a b s t r a c t Açai fruit are native to the Amazon region of South America and two predominant species are commer-cially exported as fruit pulps for use in food and beverage applications. Detailed characterisation of the polyphenolic compounds present in the de-seeded fruits of Euterpe oleracea and Euterpe precatoria species were conducted by HPLC–ESI–MS n analyses and their thermal stability and overall influence on antioxidant capacity were determined. Anthocyanins were the predominant polyphenolics in both E. oler-acea (2247 ± 23 mg/kg) and E. precatoria (3,458 ± 16 mg/kg) species, and accounted for nearly 90% of the trolox equivalent antioxidant capacity in both E. oleracea (87.4 ± 4.4 lmol TE/g) and E. precatoria (114 ± 6.9 lmol TE/g) fruits. Various flavones, including homoorientin, orientin, taxifolin deoxyhexose and isovitexin; various flavanol derivatives, including (+)-catechin, (À)-epicatechin, procyanidin dimers and trimers, and phenolic acids, including protocatechuic, p-hydroxybenzoic, vanillic, syringic and ferulic acids, were also present in both species. Thermal stability of these compounds was evaluated, following a thermal holding cycle (80 °C for up to 60 min) in the presence and absence of oxygen. Both species expe-rienced only minor changes (<5%) in non-anthocyanin polyphenolic contents during all thermal processes whereas 34 ± 2.3% of anthocyanins in E. oleracea and 10.3 ± 1.1% of anthocyanins in E. precatoria were lost under these conditions, regardless of the presence of oxygen. Proportional decreases (10–25%) in antiox-idant capacity accompanied the anthocyanin changes. Results suggest that both açai species are charac-terised by similar polyphenolic profiles, comparable antioxidant capacities, yet only moderate phytochemical stability during heating.
Fatty liver disease that develops in the absence of alcohol abuse is recognized increasingly as a major health burden. This report summarizes the presentations and discussions at a Single Topic Conference held September 20-22, 2002, and sponsored by the American Association for the Study of Liver Diseases. The conference focused on fatty liver disorders. Estimates based on imaging and autopsy studies suggest that about 20% to 30% of adults in the United States and other Western countries have excess fat accumulation in the liver. About 10% of these individuals, or fully 2% to 3% of adults, are estimated to meet current diagnostic criteria for nonalcoholic steatohepatitis (NASH). Sustained liver injury leads to progressive fibrosis and cirrhosis in a fraction, possibly up to one third, of those with NASH, and NASH may be a cause of cryptogenic cirrhosis. NASH is now a significant health issue for obese children as well, leading to cirrhosis in some. The diagnostic criteria for NASH continue to evolve and rely on the histologic findings of steatosis, hepatocellular injury (ballooning, Mallory bodies), and the pattern of fibrosis. Generally recognized indications for biopsy include establishing the diagnosis and staging of the injury, but strict guidelines do not exist. Liver enzymes are insensitive and cannot be used reliably to confirm the diagnosis or stage the extent of fibrosis. Older age, obesity, and diabetes are predictive of fibrosis. The pathogenesis of NASH is multifactorial. Insulin resistance may be an important factor in the accumulation of hepatocellular fat, whereas excess intracellular fatty acids, oxidant stress, adenosine triphosphate (ATP) depletion, and mitochondrial dysfunction may be important causes of hepatocellular injury in the steatotic liver. Efforts are underway to refine the role of insulin resistance in NASH and determine whether improving insulin sensitivity pharmacologically is an effective treatment. An altered lifestyle may be a more effective means of improving insulin sensitivity. The research agenda for the future includes establishing the role of insulin resistance and abnormal lipoprotein metabolism in NASH, determining the pathogenesis of cellular injury, defining predisposing genetic abnormalities, identifying better noninvasive predictors of disease, and defining effective therapy.
Pineapple has several beneficial properties including antioxidant activity. The fruit of pineapple was extracted with ethyl acetate, methanol and water. The phenolic content of the extracts was determined by Folin–Ciocalteu method and antioxidant activity was assayed through some in vitro models such as antioxidant capacity by phosphomolybdenum, β-carotene-linoleate, and radical scavenging activity using α,α-diphenyl-β-picrylhydrazyl (DPPH) method. The phenolic contents of the extracts as caffeic acid equivalents were found to be highest in methanol (51.1%) followed by ethyl acetate (13.8%) and water extract (2.6%). Antioxidant capacity of the extracts as equivalent to ascorbic acid (μmol/g of the extract) was in the order of methanol extract > ethyl acetate extract > water extract. In comparison with butylated hydroxyanisole (BHA), at 100 ppm of concentration, the antioxidant and free radical scavenging activities of the extracts assayed through β-carotene-linoleate and DPPH method were also found to be highest with methanol extract followed by ethyl acetate and water extracts. The results indicated that the extent of antioxidant activity of the extract is in accordance with the amount of phenolics present in that extract and the pineapple fruit being rich in phenolics may provide a good source of antioxidant.
The antiradical activities of various antioxidants were determined using the free radical, 2,2-Diphenyl-1-picrylhydrazyl (DPPH*). In its radical form. DPPH* has an absorption band at 515 nm which dissappears upon reduction by an antiradical compound. Twenty compounds were reacted with the DPPH* and shown to follow one of three possible reaction kinetic types. Ascorbic acid, isoascorbic acid and isoeugenol reacted quickly with the DPPH* reaching a steady state immediately. Rosmarinic acid and δ-tocopherol reacted a little slower and reached a steady state within 30 min. The remaining compounds reacted more progressively with the DPPH* reaching a steady state from 1 to 6 h. Caffeic acid, gentisic acid and gallic acid showed the highest antiradical activities with a stoichiometry of 4 to 6 reduced DPPH* molecules per molecule of antioxidant. Vanillin, phenol, γ-resorcylic acid and vanillic acid were found to be poor antiradical compounds. The stoichiometry for the other 13 phenolic compounds varied from one to three reduced DPPH* molecules per molecule of antioxidant. Possible mechanisms are proposed to explain the experimental results.
The anthocyanins from acerola and açai, two tropical fruits known for their bioactive compounds, were studied. Two varieties of acerola in natura and one brand of frozen pulp of açai were analyzed by high-performance liquid chromatography connected to photodiode array and mass spectrometry detectors (HPLC–PDA–MS/MS). The açai pulp presented 282–303 mg/100 g of total anthocyanin, with predominance of cyanidin 3-glucoside and cyanidin 3-rutinoside, in average proportions of 13% and 87%, respectively. The composition of the two acerola varieties (Waldy Cati 30 and Olivier) were similar, being cyanidin 3-rhamnoside (76–78%) the major anthocyanin, followed by pelargonidin 3-rhamnoside (12–15%). The acerola Waldy variety showed total anthocyanin content of 6.5–7.6 mg/100 g, while 7.9–8.4 mg/100 g were found in the Olivier variety, for fruits harvested in 2003 and 2004. No statistical differences were found between varieties and harvests for the total anthocyanin content in acerola fruits.
Açai juice at two clarity stages (semi-clarified and clarified) was compared to 100% açai pulp following ascorbic acid fortification to evaluate phytochemical and antioxidant changes during storage at 4 and 20 °C. Cyanidin-3-rutinoside (202 ± 5.8 mg/L) and cyanidin-3-glucoside (75 ± 4.8 mg/L) were the predominant anthocyanins in açai while 11 non-anthocyanin polyphenolics were detected in concentrations from 1.1 to 55 mg/L of açai pulp. Clarification of açai pulp resulted in a 27% loss in total polyphenolics (197 ± 6.9 mg gallic acid/100 mL) and in a 20% reduction in both total anthocyanins (729 ± 3.4 mg/L) and antioxidant capacity (54 ± 1.7 μmol Trolox equivalents/mL). Anthocyanin degradation followed first order kinetics, with half-lives ranging from 9.4 to 43 days for cyanidin-3-glucoside and from 18 to 82 days for cyanidin-3-rutinoside. Fortification with ascorbic acid accelerated anthocyanin degradation in clarified juice at both storage temperatures, likely due to the loss of polymeric anthocyanin forms (21%) during clarification. Although clarification enhanced the amount of monomeric anthocyanins present in açai juice which relates positively to the aesthetic quality, processing and handling regimes must be optimized to achieve maximum retention of their functional properties during storage.
Purple sweet potato is a functional food rich in anthocyanins that possess disease-preventive properties. Anthocyanins are known to possess potent antidiabetic properties. However, the effect of the anthocyanin fraction (AF) from purple sweet potato on hepatic lipid metabolism remains unclear. Our hypothesis is that AF inhibits hepatic lipid accumulation through the activation of adenosine monophosphate-activated protein kinase (AMPK) signaling pathways in vitro and in vivo. In this study, we evaluated body weight, liver histology, and hepatic lipid content in high-fat diet (HFD)-fed ICR mice treated with AF. In addition, we characterized the underlying mechanism of AF's effects in HepG2 hepatocytes through Western blot analysis. Anthocyanin fraction (200 mg/kg per day) reduced weight gain and hepatic triglyceride accumulation and improved serum lipid parameters in mice fed an HFD for 4 weeks. Anthocyanin fraction significantly increased the phosphorylation of AMPK and acetyl-coenzyme A carboxylase (ACC) in the liver and HepG2 hepatocytes. In addition, AF down-regulated the levels of sterol regulatory element-binding protein 1 and its target genes including ACC and fatty acid synthase (FAS). The specific AMPK inhibitor compound C attenuated the effects of AF on the expression of lipid metabolism-related proteins such as SREBP-1 and FAS in HepG2 hepatocytes. The beneficial effects of AF on HFD-induced hepatic lipid accumulation are thus mediated through AMPK signaling pathways, suggesting a potential target for the prevention of obesity.
Background:
Obesity induces steatosis and increases oxidative stress, as well as chronic inflammation in the liver. The balance between lipogenesis and lipolysis is disrupted in obese animals. At a cellular level, the changes in metabolic sensors and energy regulators are poorly understood. We hypothesized that diet-induced steatosis increases oxidative stress, inflammation, and changes the metabolic regulators to promote energy storage in mice. The setting was a university-affiliated basic science research laboratory.
Methods:
Four-week-old C57BL mice were fed a high-fat diet (n = 8) or regular chow (n = 8) for 7 weeks. The liver sections were stained for fat content and immunofluorescence. Liver homogenates were used for protein analysis by immunoblotting and mRNA analysis by reverse transcriptase-polymerase chain reaction. The gels were quantified using densitometry P ≤ .05 was considered significant.
Results:
The high-fat diet upregulated protein kinase-C atypical isoforms ζ and λ and decreased glucose tolerance and the interaction of insulin receptor substrate 2 with phosphoinositide kinase-3. The high-fat diet increased the transcriptional factors liver X receptor (4321 ± 98 versus 2981 ± 80) and carbohydrate response element-binding protein (5132 ± 135 versus 3076 ± 91), the lipogenesis genes fatty acid binding protein 5, stearoyl-co-enzyme A desaturase-1, and acetyl-co-enzyme A carboxylase protein, and fatty acid synthesis. The high-fat diet decreased 5'-adenosine monophosphate-activated protein kinase (2561 ± 78 versus 1765 ± 65), glucokinase-3β (2.214 ± 34 versus 3356 ± 86), and SIRT1 (2015 ± 76 versus 3567 ± 104) and increased tumor necrosis factor-α (3415 ± 112 versus 2042 ± 65), nuclear factor kappa B (5123 ± 201 versus 2562 ± 103), cyclooxygenase-2 (4230 ± 113 versus 2473 ± 98), nicotinamide-adenine dinucleotide phosphate oxidase (3501 ± 106 versus 1600 ± 69) and reactive oxygen species production (all P < .001, obese mice versus lean mice).
Conclusion:
A high-fat diet impairs glucose tolerance and hepatic insulin signaling, upregulates transcriptional and translational activities that promote lipogenesis, cytokine production, proinflammatory signaling, and oxidative stress, and downregulates lipolysis. Understanding the complex cellular signals triggered by obesity might have profound clinical implications.
Obesity is a major risk factor for the development of type 2 diabetes, and both conditions are now recognized to possess significant inflammatory components underlying their pathophysiologies. Here, we hypothesized that cyanidin 3-glucoside (C3G), a typical anthocyanin reported to possess potent anti-inflammatory properties, would ameliorate obesity-associated inflammation and metabolic disorders, such as insulin resistance and hepatic steatosis in mouse models of diabesity. Male C57BL/6J obese mice fed a high-fat diet for 12 weeks and genetically diabetic db/db mice at an age of 6 weeks received dietary C3G supplementation (0.2%) for 5 weeks. We found that dietary C3G lowered fasting glucose levels and markedly improved the insulin sensitivity in both high-fat diet fed and db/db mice as compared with unsupplemented controls. White adipose tissue messenger RNA levels and serum concentrations of inflammatory cytokines (tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1) were reduced by C3G, as did macrophage infiltration in adipose tissue. Concomitantly, hepatic triglyceride content and steatosis were alleviated by C3G. Moreover, C3G treatment decreased c-Jun N-terminal kinase activation and promoted phosphorylation and nuclear exclusion of forkhead box O1 after refeeding. These findings clearly indicate that C3G has significant potency in antidiabetic effects by modulating the c-Jun N-terminal kinase/forkhead box O1 signaling pathway and the related inflammatory adipocytokines.
We investigated the antioxidant potential and hypocholesterolemic effects of acai (Euterpe oleracea Mart.) pulp ingestion in rats fed a standard or hypercholesterolemic diet.
Female Fischer rats were fed a standard AIN-93 M diet (control) or a hypercholesterolemic diet that contained 25% soy oil and 1% cholesterol. The test diet was supplemented with 2% acai pulp (dry wt/wt) for control (group CA) and hypercholesterolemic rats (group HA) for 6 wk. At the end of the experimental period, rats were sacrificed and the blood and livers were collected. To evaluate the effect of acai consumption, levels of protein carbonyl and sulfhydryl groups, superoxide dismutase and paraoxonase activities, and lipid profiles of the sera were measured.
Animals that were fed the hypercholesterolemic diet presented increased levels of total and non-high-density lipoprotein cholesterol and decreased levels of high-density lipoprotein cholesterol. Supplementing the diet of this group with acai caused a hypocholesterolemic effect by reducing total and non-high-density lipoprotein cholesterol. Serum levels of carbonyl proteins and total, free, and protein sulfhydryl groups were reduced by acai ingestion in animals receiving the standard or hypercholesterolemic diet. Acai supplementation induced a significant reduction in superoxide dismutase activity only in the hypercholesterolemic rats, indicating an association between diet and acai treatment. Also, acai supplementation increased paraoxonase activity in the CA and HA groups.
These results suggest that the consumption of acai improves antioxidant status and has a hypocholesterolemic effect in an animal model of dietary-induced hypercholesterolemia.
Açai, the fruit of a palm native to the Amazonian basin, is widely distributed in northern South America, where it has considerable economic importance. Whereas individual polyphenolics compounds in açai have been extensively evaluated, studies of the intact fruit and its biological properties are lacking. Therefore, the present study was undertaken to investigate the in vivo genotoxicity of açai and its possible antigenotoxicity on doxorubicin (DXR)-induced DNA damage. The açai pulp doses selected were 3.33, 10.0 and 16.67g/kg b.w. administered by gavage alone or prior to DXR (16mg/kg b.w.) administered by intraperitoneal injection. Swiss albino mice were distributed in eight groups for acute treatment with açai pulp (24h) and eight groups for subacute treatment (daily for 14 consecutive days) before euthanasia. The negative control groups were treated in a similar way. The results of chemical analysis suggested the presence of carotenoids, anthocyanins, phenolic, and flavonoids in açai pulp. The endpoints analyzed were micronucleus induction in bone marrow and peripheral blood cells polychromatic erythrocytes, and DNA damage in peripheral blood, liver and kidney cells assessed using the alkaline (pH >13) comet assay. There were no statistically significant differences (p>0.05) between the negative control and the groups treated with the three doses of açai pulp alone in all endpoints analyzed, demonstrating the absence of genotoxic effects. The protective effects of açai pulp were observed in both acute and subacute treatments, when administered prior to DXR. In general, subacute treatment provided greater efficiency in protecting against DXR-induced DNA damage in liver and kidney cells. These protective effects can be explained as the result of the phytochemicals present in açai pulp. These results will be applied to the developmental of food with functional characteristics, as well as to explore the characteristics of açai as a health promoter.
Non-alcoholic fatty liver disease (NAFLD) represents a wide spectrum of diseases, ranging from simple fatty liver (hepatic steatosis) through steatosis with inflammation and necrosis to cirrhosis. NAFLD, which is strongly associated with obesity, insulin resistance and type 2 diabetes, is now well recognized as being part of the metabolic syndrome. The metabolic pathways leading to the development of hepatic steatosis are multiple, including enhanced non-esterified fatty acid release from adipose tissue (lipolysis), increased de novo fatty acids (lipogenesis) and decreased beta-oxidation. Recently, several mouse models have helped to clarify the molecular mechanisms leading to the development of hepatic steatosis in the pathogenesis of NAFLD. This review describes the models that have provided evidence implicating lipogenesis in the development and/or prevention of hepatic steatosis.
Adiponectin and adiponectin receptors (AdipoRs) have been found to play significant roles in the etiology of obesity-related chronic disease. Their discovery has been a long and complicated path, with many challenges. Developing methods to unravel the molecular secrets has been an informative process in itself. However, with both functional and genetic studies confirming adiponectin as a therapeutic target adipokine, many roles and interactions with certain other biomolecules have been clearly defined. We have found that decreased high molecular weight (HMW) adiponectin plays a crucial and causal role in obesity-linked insulin resistance and metabolic syndrome; that AdipoR1 and AdipoR2 serve as the major AdipoRs in vivo; and that AdipoR1 activates the AMP kinase (AMPK) pathway and AdipoR2, the peroxisome proliferator-activated receptor alpha (PPARalpha) pathway in the liver, to increase insulin sensitivity and decrease inflammation. Further conclusions are that decreased adiponectin action and increased monocyte chemoattractant protein-1 (MCP-1) form a vicious adipokine network causing obesity-linked insulin resistance and metabolic syndrome; PPARgamma upregulates HMW adiponectin and PPARalpha upregulates AdipoRs; that dietary osmotin can serve as a naturally occurring adiponectin receptor agonist; and finally, that under starvation conditions, MMW adiponectin activates AMPK in hypothalamus, and promotes food intake, and at the same time HMW adiponectin activates AMPK in peripheral tissues, such as skeletal muscle, and stimulates fatty-acids combustion. Importantly, under pathophysiological conditions, such as obesity and diabetes, only HMW adiponectin was decreased; therefore, strategies to increase only HMW adiponectin may be a logical approach to provide a novel treatment modality for obesity-linked diseases, such as insulin resistance and type 2 diabetes. It is hoped that these data will be helpful in developing treatments to counteract the destructive, expensive and painful effects of obesity.
Unlabelled:
Adiponectin is an adipocyte-derived hormone with a wide range of beneficial effects on obesity-related medical complications. Numerous epidemiological investigations in diverse ethnic groups have identified a lower adiponectin level as an independent risk factor for nonalcoholic fatty liver diseases and liver dysfunctions. Animal studies have demonstrated that replenishment of adiponectin protects against various forms of hepatic injuries, suggesting it to be a potential drug candidate for the treatment of liver diseases. This study was designed to investigate the cellular and molecular mechanisms underlying the hepatoprotective effects of adiponectin. Our results demonstrated that in adiponectin knockout (ADN-KO) mice, there was a preexisting condition of hepatic steatosis and mitochondrial dysfunction that might contribute to the increased vulnerabilities of these mice to secondary liver injuries induced by obesity and other conditions. Adenovirus-mediated replenishment of adiponectin depleted lipid accumulation, restored the oxidative activities of mitochondrial respiratory chain (MRC) complexes, and prevented the accumulation of lipid peroxidation products in ADN-KO mice but had no obvious effects on mitochondrial biogenesis. The gene and protein levels of uncoupling protein 2 (UCP2), a mitochondrial membrane transporter, were decreased in ADN-KO mice and could be significantly up-regulated by adiponectin treatment. Moreover, the effects of adiponectin on mitochondrial activities and on protection against endotoxin-induced liver injuries were significantly attenuated in UCP2 knockout mice.
Conclusion:
These results suggest that the hepatoprotective properties of adiponectin are mediated at least in part by an enhancement of the activities of MRC complexes through a mechanism involving UCP2.
The steady-state basal plasma glucose and insulin concentrations are determined by their interaction in a feedback loop. A computer-solved model has been used to predict the homeostatic concentrations which arise from varying degrees beta-cell deficiency and insulin resistance. Comparison of a patient's fasting values with the model's predictions allows a quantitative assessment of the contributions of insulin resistance and deficient beta-cell function to the fasting hyperglycaemia (homeostasis model assessment, HOMA). The accuracy and precision of the estimate have been determined by comparison with independent measures of insulin resistance and beta-cell function using hyperglycaemic and euglycaemic clamps and an intravenous glucose tolerance test. The estimate of insulin resistance obtained by homeostasis model assessment correlated with estimates obtained by use of the euglycaemic clamp (Rs = 0.88, p less than 0.0001), the fasting insulin concentration (Rs = 0.81, p less than 0.0001), and the hyperglycaemic clamp, (Rs = 0.69, p less than 0.01). There was no correlation with any aspect of insulin-receptor binding. The estimate of deficient beta-cell function obtained by homeostasis model assessment correlated with that derived using the hyperglycaemic clamp (Rs = 0.61, p less than 0.01) and with the estimate from the intravenous glucose tolerance test (Rs = 0.64, p less than 0.05). The low precision of the estimates from the model (coefficients of variation: 31% for insulin resistance and 32% for beta-cell deficit) limits its use, but the correlation of the model's estimates with patient data accords with the hypothesis that basal glucose and insulin interactions are largely determined by a simple feed back loop.
To investigate the role of diet as a predictor of glucose intolerance and non-insulin-dependent diabetes mellitus (NIDDM).
At the 30-year follow-up survey of the Dutch and Finnish cohorts of the Seven Countries Study, in 1989/1990, men were examined according to a standardized protocol including a 2-h oral glucose tolerance test. Information on habitual food consumption was obtained using the cross-check dietary history method. Those 338 men in whom information on habitual diet was also available 20 years earlier were included in this study. Subjects known as having diabetes in 1989/1990 were excluded from the analyses.
Adjusting for age and cohort, the intake of total, saturated, and monounsaturated fatty acids and dietary cholesterol 20 years before diagnosis was higher in men with newly diagnosed diabetes in the survey than in men with normal or impaired glucose tolerance. After adjustment for cohort, age, past body mass index, and past energy intake, the past intake of total fat was positively associated with 2-h postload glucose level (P < 0.05). An independent inverse association with the past intake of vitamin C was observed (P < 0.05). These associations were independent of changes in the intake of fat and vitamin C during the 20-year follow-up. An increase in the consumption of vegetables and legumes, potatoes, and fish during the 20-year follow-up was inversely related with 2-h glucose level (P < 0.05).
Although the regression coefficients were in general not very large, these results indicate that a high intake of fat, especially that of saturated fatty acids, contributes to the risk of glucose intolerance and NIDDM. Foods such as fish, potatoes, vegetables, and legumes may have a protective effect. In addition, the observed inverse association between vitamin C and glucose intolerance suggests that antioxidants may also play a role in the development of derangements in glucose metabolism.
Adipose differentiation is accompanied by changes in cellular morphology, a dramatic accumulation of intracellular lipid and activation of a specific program of gene expression. Using an mRNA differential display technique, we have isolated a novel adipose cDNA, termed adipoQ. The adipoQ cDNA encodes a polypeptide of 247 amino acids with a secretory signal sequence at the amino terminus, a collagenous region (Gly-X-Y repeats), and a globular domain. The globular domain of adipoQ shares significant homology with subunits of complement factor C1q, collagen alpha 1(X), and the brain-specific factor cerebellin. The expression of adipoQ is highly specific to adipose tissue in both mouse and rat. Expression of adipoQ is observed exclusively in mature fat cells as the stromal-vascular fraction of fat tissue does not contain adipoQ mRNA. In cultured 3T3-F442A and 3T3-L1 preadipocytes, hormone-induced differentiation dramatically increases the level of expression for adipoQ. Furthermore, the expression of adipoQ mRNA is significantly reduced in the adipose tissues from obese mice and humans. Whereas the biological function of this polypeptide is presently unknown, the tissue-specific expression of a putative secreted protein suggests that this factor may function as a novel signaling molecule for adipose tissue.
There is no known treatment for fatty liver, a ubiquitous cause of chronic liver disease. However, because it is associated with hyperinsulinemia and insulin-resistance, insulin-sensitizing agents might be beneficial. To evaluate this possibility, insulin-resistant ob/ob mice with fatty livers were treated with metformin, an agent that improves hepatic insulin-resistance. Metformin improved fatty liver disease, reversing hepatomegaly, steatosis and aminotransferase abnormalities. The therapeutic mechanism likely involves inhibited hepatic expression of tumor necrosis factor (TNF) alpha and TNF-inducible factors that promote hepatic lipid accumulation and ATP depletion. These findings suggest a mechanism of action for metformin and identify novel therapeutic targets in insulin-resistant states.
Adiponectin is an adipocyte-derived hormone. Recent genome-wide scans have mapped a susceptibility locus for type 2 diabetes and metabolic syndrome to chromosome 3q27, where the gene encoding adiponectin is located. Here we show that decreased expression of adiponectin correlates with insulin resistance in mouse models of altered insulin sensitivity. Adiponectin decreases insulin resistance by decreasing triglyceride content in muscle and liver in obese mice. This effect results from increased expression of molecules involved in both fatty-acid combustion and energy dissipation in muscle. Moreover, insulin resistance in lipoatrophic mice was completely reversed by the combination of physiological doses of adiponectin and leptin, but only partially by either adiponectin or leptin alone. We conclude that decreased adiponectin is implicated in the development of insulin resistance in mouse models of both obesity and lipoatrophy. These data also indicate that the replenishment of adiponectin might provide a novel treatment modality for insulin resistance and type 2 diabetes.
Anthocyanin and polyphenolic compounds present in açai (Euterpe oleracea Mart.) were determined and their respective contribution to the overall antioxidant capacity established. Color stability of açai anthocyanins against hydrogen peroxide (0 and 30 mmol/L) over a range of temperatures (10-30 degrees C) was also determined and compared to common anthocyanin sources. Additionally, stability in a model beverage system was evaluated in the presence of ascorbic acid and naturally occurring polyphenolic cofactors. Cyanidin 3-glucoside (1040 mg/L) was the predominant anthocyanin in açai and correlated to antioxidant content, while 16 other polyphenolics were detected from 4 to 212 mg/L. Red grape anthocyanins were most stable in the presence of hydrogen peroxide, while açai and pigments rich in acylated anthocyanins displayed lower color stability in a temperature-dependent manner. In the presence of ascorbic acid, acylated anthocyanin sources generally had increased color stability. Açai was recognized for its functional properties for use in food and nutraceutical products.
Adiponectin has antilipogenic and anti-inflammatory effects, while tumor necrosis factor alpha (TNF-alpha) reduces insulin sensitivity and has proinflammatory effects. We examined (1) the extent to which hypoadiponectinemia and TNF-alpha activation are features of nonalcoholic steatohepatitis (NASH) and (2) whether serum levels of these markers correlate with the severity of histological changes in 109 subjects with nonalcoholic fatty liver disease (NAFLD), including 80 with NASH and 29 with simple steatosis. By multivariate analysis, subjects with NASH had reduced adiponectin level and increased TNF-alpha and soluble TNF receptor 2 (sTNFR2)-but not leptin levels, compared with controls matched by age, sex, and body mass index; these differences were independent of the increased insulin resistance (by homeostasis model [HOMA-IR]) in NASH. When compared with simple steatosis, NASH was associated with lower adiponectin levels and higher HOMA-IR, but there were no significant differences in the levels of TNF-alpha and sTNFR2. The majority of subjects with steatohepatitis (77%) had adiponectin levels less than 10 microg/mL and HOMA-IR greater than 3 units, but only 33% of those with pure steatosis had these findings. HOMA-IR and low serum adiponectin were also independently associated with increased grades of hepatic necroinflammation. In conclusion, hypoadiponectinemia is a feature of NASH independent of insulin resistance. Reduced adiponectin level is associated with more extensive necroinflammation and may contribute to the development of necroinflammatory forms of NAFLD.