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Wild blueberry (Vaccinium angustifolium)-enriched diet improves dyslipidaemia and modulates the expression of genes related to lipid metabolism in obese Zucker rats
Abstract
The present study investigated the potential of a wild blueberry (WB)-enriched diet to improve blood lipid profile and modulate the expression of genes related to lipid homeostasis in obese Zucker rats (OZR), a model of the metabolic syndrome with severe dyslipidaemia. For this purpose, twenty OZR and twenty lean Zucker rats (LZR; controls) were placed either on a control (C) or an 8 % WB diet for 8 weeks. Plasma total cholesterol (TC), HDL-cholesterol and TAG concentrations were determined. The relative expression of six genes involved in lipid metabolism was also determined in both the liver and the abdominal adipose tissue (AAT). Plasma TAG and TC concentrations were significantly lower in the OZR following WB consumption (4228 (sem 471) and 2287 (sem 125) mg/l, respectively) than in those on the C diet (5475 (sem 315) and 2631 (sem 129) mg/l, P< 0·05), while there was no change in HDL-cholesterol concentration. No significant effects were observed for plasma lipids in the LZR. Following WB consumption, the expression of the transcription factors PPARα and PPARγ in the OZR was increased in the AAT, while that of sterol regulatory element-binding protein 1 (SREBP-1) was decreased in the liver and AAT. The expression of fatty acid synthase was significantly decreased in both the liver and AAT and that of ATP-binding cassette transporter 1 was increased in the AAT following WB consumption. In conclusion, WB consumption appears to improve lipid profiles and modulate the expression of key enzymes and transcription factors of lipid metabolism in severely dyslipidaemic rats.
... Among all berries, the bilberries (BiB; Vaccinium myrtillus) and blueberries (BB; Vaccinium spp.) have the most diverse profile of anthocyanins, and BiB, specifically, has the highest content of anthocyanins [15]. Studies in humans have shown that consumption of BiB and BB can improve blood pressure (BP) [16], insulin sensitivity [17], and lipid metabolism [18][19][20][21], and it also reduces inflammatory [19,22] and oxidative stress [16,22] markers. Accordingly, in animal studies, BiB and BB consumption also seems to improve lipid [22][23][24][25] and glucose metabolisms [24,26,27] and reduce inflammation [22,[28][29][30] and oxidative stress [28,29,[31][32][33]. ...
... However, after full-text analysis, 72 articles were excluded because of the use of pomace or leaf extracts instead of the whole fruit, as well as the use of purified anthocyanins or conference abstracts. Therefore, a total of 29 articles fulfilled the eligibility criteria [16][17][18][19][20][21][22][23][24][26][27][28][29][30]32,33,[35][36][37][38][43][44][45][46][47][48][49][50][51]. Moreover, two articles were identified by a manual search of the reference lists of the 29 articles [31,34], totalizing 31 articles. ...
... Moreover, two articles were identified by a manual search of the reference lists of the 29 articles [31,34], totalizing 31 articles. Among the included studies, eight were clinical trials [16][17][18][19]22,43,46,47], 10 used animal models with rats [21,23,26,28,30,32,33,35,38,49], 12 were animal models with mice [20,24,27,29,34,36,37,44,45,48,50,51], and one study included Guinea pigs [31]. ...
Low-grade inflammation and oxidative stress are key mechanisms involved in obesity and related disorders. Polyphenols from blueberry (BB) and bilberries (BiB) might protect against oxidative damage and inflammation. To summarize the effects of BiB or BB consumption in parameters related to obesity and its comorbidities, a search of the literature was performed in PubMed, Embase, and Cochrane Library repositories to identify all studies that evaluated associations of whole BB or BiB with obesity and associated disorders. Thirty-one studies were eligible for inclusion in this review: eight clinical trials and 23 animal studies. In humans, BB consumption only consistently decreased oxidative stress and improved endothelial function. In rodents, BB or BiB consumption caused positive effects on glucose tolerance, nuclear factor-kappa B (Nf-κb) activity, oxidative stress, and triglyceride (TG) content in the liver and hepatic steatosis. The high content of anthocyanins present in BB and BiB seems to attenuate oxidative stress. The decrease in oxidative stress may have a positive impact on glucose tolerance and endothelial function. Moreover, in rodents, these berries seem to protect against hepatic steatosis, through the decreased accumulation of hepatic TGs. BB and BiB might also attenuate inflammation by decreasing Nf-κb activity and immune cell recruitment into the adipose tissue.
... Wild blueberries contain anthocyanin, an antioxidant polyphenol. When stout and skinny Zucker rats were fed a wild blueberry-enriched diet for eight weeks, the corpulent Zucker rats demonstrated an increase in dyslipidemia and changes in lipid digesting system features [97]. The stout group had considerably reduced levels of triacylglycerol (TAG) and triacylcarnitine (TC), but not the lean group. ...
... Insulin resistance is improved [100,110], the appetite is suppressed [76], and lipid metabolism is regulated by Vaccicum spp. [97]. Blueberry anthocyanins could be useful in the treatment of obesity and diabetes. ...
... Food intake, body weight gain, body fat, and blood glucose levels were all reduced by blueberry water extract, which also activated PPARs [77]. Furthermore, anthocyanins found in V. angustifolium (wild blueberry) ameliorate dyslipidemia via modulating the genes involved in lipid metabolism [97]. ...
Obesity and diabetes are the most demanding health problems today, and their prevalence, as well as comorbidities, is on the rise all over the world. As time goes on, both are becoming big issues that have a big impact on people’s lives. Diabetes is a metabolic and endocrine illness set apart by hyperglycemia and glucose narrow-mindedness because of insulin opposition. Heftiness is a typical, complex, and developing overall wellbeing worry that has for quite some time been connected to significant medical issues in individuals, all things considered. Because of the wide variety and low adverse effects, herbal products are an important hotspot for drug development. Synthetic compounds are not structurally diverse and lack drug-likeness properties. Thus, it is basic to keep on exploring herbal products as possible wellsprings of novel drugs. We conducted this review of the literature by searching Scopus, Science Direct, Elsevier, PubMed, and Web of Science databases. From 1990 until October 2021, research reports, review articles, and original research articles in English are presented. It provides top to bottom data and an examination of plant-inferred compounds that might be utilized against heftiness or potentially hostile to diabetes treatments. Our expanded comprehension of the systems of activity of phytogenic compounds, as an extra examination, could prompt the advancement of remedial methodologies for metabolic diseases. In clinical trials, a huge number of these food kinds or restorative plants, as well as their bioactive compounds, have been shown to be beneficial in the treatment of obesity.
... Several in vivo studies highlighted the antioxidant and anti-inflammatory effects of BB and its specific compounds on metabolic impairments. An overall improvement in the inflammatory status was reported in obese Zucker rats supplemented with wild BB powder [126]. The consumption of 8% wild blueberry-enriched diet for 8 weeks significantly decreased plasma levels of TNF-α, IL-6 and CRP and increased adiponectin. ...
... The consumption of 8% wild blueberry-enriched diet for 8 weeks significantly decreased plasma levels of TNF-α, IL-6 and CRP and increased adiponectin. In addition, the expression of CRP was reduced in the liver, while TNF-α, IL-6 and NF-κB were down-regulated in both liver and abdominal adipose tissue [126]. In male Wistar rats, BB supplementation in the diet elicited the normalization of TNF-α and IL-1β levels, which were increased by 300% and 500% due to a high-fat feeding paradigm [127]. ...
... In addition, an enhanced phosphorylation of acetyl-CoA carboxylase (ACC), the key enzyme for FA synthesis that is downstream of AMPK, and the upregulation of PPAR-α, acyl-CoA oxidase (ACO) and CPT1, were found in the liver of diabetic mice supplemented with BBE. Furthermore, supplementation of BB polyphenols extracts also decreased the hepatic mRNA expression of SREBP-1 and fatty acid synthase (FAS), which could contribute to improved hepatic lipid metabolism [126]. Other recent findings suggest that phenolic BB extract improved hepatic lipid metabolism via pathways involving the bile acids receptors farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5) [33]. ...
Prediabetes, a subclinical impairment between euglycemia and hyperglycemia, is a risk factor for the development of type 2 diabetes mellitus (T2DM) and associated micro- and macrovascular complications. Lifestyle therapy, the first-line treatment of prediabetes, includes physical exercise and dietary regimens enriched in phytochemicals with health-related properties. Blueberries (Vaccinium spp.), given their pleasant taste and great abundance in beneficial phytochemicals, have gained public interest all over the world. Along with a high antioxidant activity, this functional fruit is also well-recognized due to its hypoglycemic and insulin-sensitizing effects and has been recommended for overt T2DM management. Yet blueberries target several other pathophysiological traits, namely gut microbiota dysbiosis and hepatic dysmetabolism, that ensue when prediabetes begins and for which pharmacological interventions tend to be delayed. In this work, we revisited preclinical data from in vitro assays, animal models and human studies, aiming to disclose the potential mechanisms by which blueberries may be a fruitful source of phytochemicals able to prevent (pre)diabetes progression. Collectively, future efforts should focus on longer-term studies with standardized interventions and readouts, particularly in humans, that will hopefully bring more robust evidence and concrete guidance for blueberries’ effective use in prediabetes.
... Red raspberries are gaining nutritional interest due to their unique bioactive profiles, with a particularly high level of the polyphenol ellagitannin which has been documented to physiologically benefit cardiovascular health (10). Previous studies in the Klimis-Zacas laboratory have demonstrated the efficacy of a wild blueberry-enriched diet in the attenuation of obesityinduced inflammation, through successfully decreasing PVAT expression and concentration of inflammatory markers in the obese Zucker rat (OZR), a model of MetS (11)(12)(13)(14). ...
... In a study that placed obese rats on a calorie-restricted diet which led to weight loss, the PVAT damage that was initially present in rats during obesity was reversed through a reduction in inflammation and increase in nitric oxide synthetase activity (130). This is evidence of the positive impact (11)(12)(13)(14). This improvement took place through a decrease in inflammatory marker expression, improved lipid profiles, normalized vascular function, and modulated oxidative stress (11)(12)(13)(14). ...
... This is evidence of the positive impact (11)(12)(13)(14). This improvement took place through a decrease in inflammatory marker expression, improved lipid profiles, normalized vascular function, and modulated oxidative stress (11)(12)(13)(14). ...
The Metabolic Syndrome (MetS) affects 35% of U.S. adults and is an indicator of early death. While pharmacological treatments have been developed for the majority of MetS risk factors, obesity-induced inflammation remains to be addressed. Dysfunctional adipose tissue is a source of inflammation, and perivascular adipose tissue (PVAT) is critical in its pathogenesis. This study investigates the effects of red raspberry (rubus idaeus) diet-enrichment on inflammation of PVAT. The obese Zucker rat (OZR) model of MetS and the lean Zucker rat (LZR) control (C) model were used. Rats received an eight-week control or whole red raspberry-enriched (WRR) diet (8% w/w red raspberry powder). RT-PCR was performed on LZR and OZR PVAT homogenates to determine gene expression of pro-inflammatory markers (IL-1β, IL-6, MCP- 1, NF- κB, TNF- α) and anti-inflammatory markers (adiponectin and IL-10), and ELISAs were performed to determine concentrations of a subset of these markers (adiponectin, IL-1β, IL-10, MCP-1). RT-PCR analyses of PVAT indicated a significant down-regulation of pro-inflammatory marker NF-κB in OZR-C versus LZR-C models. ELISA analyses indicated a significant increase in anti-inflammatory marker adiponectin concentration in OZR-WRR versus OZR-C models, a significant decrease in anti-inflammatory marker IL-10 concentration in OZR-C versus LZR-C models, and a significant decrease in pro-inflammatory marker IL-1β concentration in OZR-C versus LZR-C models. Findings suggest that WRR enrichment does not have a consistent genomic or proteomic effect on PVAT inflammation status. Further investigations are needed to elucidate the molecular mechanisms dictating the pro-inflammatory and anti-inflammatory effects observed.
... The utilization of a diet rich in polyphenol compounds may minimize the complications of metabolic disorders. Since the polyphenolic compounds, including proanthocyanidins, have strong antioxidant properties, they can protect against oxidative stress (Vendrame et al., 2014). ...
... Diets that are enriched in blueberries reportedly improve dyslipidaemia, and in a previous study, plasma TG and total cholesterol (TC) concentrations were significantly reduced in rats treated with blueberry extract (Vendrame et al., 2014). The antidyslipidaemic effects of blueberries include increased expression of key enzymes, such as lipoprotein lipase (LPL) and fatty acid synthase (Wei et al., 2011), which are involved in TG and cholesterol metabolism. ...
... The antidyslipidaemic effects of blueberries include increased expression of key enzymes, such as lipoprotein lipase (LPL) and fatty acid synthase (Wei et al., 2011), which are involved in TG and cholesterol metabolism. Furthermore, sterol regulatory element-binding transcription factor (SREBP) and peroxisome proliferator-activated receptor (PPAR) were associated with the effects of blueberry consumption on lipid profiles (Vendrame et al., 2014), and consumption of 1%, 2% and 4% blueberry-supplements for 8 weeks significantly reduced TC and LDL-C concentrations in pigs (Kalt et al., 2008). ...
Radiation exposure is known to produce many harmful effects in biological systems, and these effects are often mediated by oxygen free radicals. Because blueberries are rich in antioxidant compounds such as anthocyanins and phenolic acids, we divided forty adult rats into four treatment groups of 10 (G1–4) as follows: G1 rats were used as a control, G2 rats were irradiated with 8 Gy at 2 Gy/week at a dose rate of 0.5 Gy/min, G3 rats were administered blueberry extract (200 mg/kg) and G4 rats were administered blueberry extract during the same irradiation period. In subsequent determinations, γ-irradiated rats had increased levels of cholesterol, triglyceride, high density lipoprotein (HDL) and low density lipoprotein (LDL), and significantly elevated liver enzyme activities, including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), and total bilirubin. In contrast, significant reductions in albumin, total protein and globulin were observed, whereas gamma irradiation decreased activities of the antioxidant enzymes glutathione (GSH), catalase (CAT), xanthine dehydrogenase (XDH) and superoxide dismutase (SOD). We also observed incremental increases in DNA fragmentation percentages and histopathological changes in liver tissues. Serum pro-inflammatory cytokine levels (IL-6, IL-10 and TNF-α) were significantly elevated and hepatic NF-кB was upregulated. In G4 rats, treatments with blueberry extract restored liver pro-oxidant status, reduced cytokine levels, ameliorated histopathological parameters and reduced DNA damage. In conclusion, γ-radiation exerts toxic effects in the rat livers, and blueberry extract is protective against these.
... Diets enriched with blueberries have been reported to improve dyslipidaemia (Seymour et al., 2009(Seymour et al., , 2011Vendrame, Daugherty, Kristo, & Klimis-Zacas, 2014;Wu et al., 2013). Plasma TG and total cholesterol (TC) concentrations were significantly reduced in Obese Zucker rats supplemented with 8% wild blueberry for 8 weeks (Vendrame et al., 2014) or 2% blueberry powder for 13 weeks in both LFD and HFD groups compared with the control groups (Seymour et al., 2009). ...
... Diets enriched with blueberries have been reported to improve dyslipidaemia (Seymour et al., 2009(Seymour et al., , 2011Vendrame, Daugherty, Kristo, & Klimis-Zacas, 2014;Wu et al., 2013). Plasma TG and total cholesterol (TC) concentrations were significantly reduced in Obese Zucker rats supplemented with 8% wild blueberry for 8 weeks (Vendrame et al., 2014) or 2% blueberry powder for 13 weeks in both LFD and HFD groups compared with the control groups (Seymour et al., 2009). These observations were also supported by a reduction in serum TC and low density lipoprotein cholesterol (LDL-C), as well as the levels of liver TG and TC following consumption of blueberry juice. ...
... The possible pathways involved in the anti-dyslipidaemic effect of blueberries include the regulation and expression of key enzymes such as lipoprotein lipase (LPL) (Wei et al., 2011), fatty acid synthase (Tsuda, Ueno, Kojo, Yoshikawa, & Osawa, 2005) and ATP-binding cassette transporter 1 (ABCA1) (Xia et al., 2005) which are involved in TG and cholesterol metabolism. Furthermore, the expression of transcription factors such as sterol regulatory element-binding transcription factor (SREBP) and peroxisome proliferator-activated receptor (PPAR) in bioactive tissues could also explain the observed effects of blueberry consumption on lipid profiles (Cutler, Petersen, & Anandh Babu, 2016;Vendrame et al., 2014). In a recent study, the expression of PPARa and PPARc in Obese Zucker rats were increased in the abdominal adipose tissue (AAT), while that of total SREBP-1 was decreased in both the liver and the AAT of the rats following consumption of a diet enriched with 8% wild blueberry for 8 weeks (Vendrame et al., 2014). ...
Recent experimental and clinical studies suggest that consumption of blueberry products has potential health benefits in ameliorating the development of obesity and its related comorbidities, including type 2 diabetes (T2D) and chronic inflammation. Blueberry fruits are enriched with numerous bioactive components such as vitamins, phenolic acid and anthocyanins which could contribute to these protective effects. Possible mechanisms by which blueberries exert their beneficial properties include counteracting oxidative stress, regulating glucose metabolism, improving lipid profile, and lowering inflammatory cytokine levels in animal models and preliminary human trials. This review focuses on the potential role of blueberries as a functional food in the prevention and treatment of obesity and its comorbidities. Although the current evidence is promising, further randomized controlled studies in the longer term are needed to evaluate the role of blueberries and blueberry extracts to support human health.
... Several studies have reported the positive effects of blueberry-enriched diets on dyslipidemia [26,[39][40][41], describing a reduction in TC and LDL-c levels in obese Zucker rats supplemented with 8% wild blueberry during 8 weeks [41] and with 2% blueberry powder for 13 weeks [40], and a decrease in TC and LDL-c contents in Wistar rats under BJ treatment for 14 weeks [26]. In contrast with those findings, we observed that BJ not only failed to attenuate the HFD-induced increase in LDL-c levels, but also further increased the serum TC and TGs levels. ...
... Several studies have reported the positive effects of blueberry-enriched diets on dyslipidemia [26,[39][40][41], describing a reduction in TC and LDL-c levels in obese Zucker rats supplemented with 8% wild blueberry during 8 weeks [41] and with 2% blueberry powder for 13 weeks [40], and a decrease in TC and LDL-c contents in Wistar rats under BJ treatment for 14 weeks [26]. In contrast with those findings, we observed that BJ not only failed to attenuate the HFD-induced increase in LDL-c levels, but also further increased the serum TC and TGs levels. ...
Blueberries, red fruits enriched in polyphenols and fibers, are envisaged as a promising nutraceutical intervention in a plethora of metabolic diseases. Prediabetes, an intermediate state between normal glucose tolerance and type 2 diabetes, fuels the development of complications, including hepatic steatosis. In previous work, we have demonstrated that blueberry juice (BJ) supplementation benefits glycemic control and lipid profile, which was accompanied by an amelioration of hepatic mitochondrial bioenergetics. The purpose of this study is to clarify the impact of long-term BJ nutraceutical intervention on cellular mechanisms that govern hepatic lipid homeostasis, namely autophagy and endoplasmic reticulum (ER) stress, in a rat model of prediabetes. Two groups of male Wistar rats, 8-weeks old, were fed a prediabetes-inducing high-fat diet (HFD) and one group was fed a control diet (CD). From the timepoint where the prediabetic phenotype was achieved (week 16) until the end of the study (week 24), one of the HFD-fed groups was daily orally supplemented with 25 g/kg body weight (BW) of BJ (HFD + BJ). BW, caloric intake, glucose tolerance and insulin sensitivity were monitored throughout the study. The serum and hepatic lipid contents were quantified. Liver and interscapular brown and epidydimal white adipose tissue depots (iBAT and eWAT) were collected for histological analysis and to assess thermogenesis, ER stress and autophagy markers. The gut microbiota composition and the short-chain fatty acids (SCFAs) content were determined in colon fecal samples. BJ supplementation positively impacted glycemic control but was unable to prevent obesity and adiposity. BJ-treated animals presented a reduction in fecal SCFAs, increased markers of arrested iBAT thermogenesis and energy expenditure, together with an aggravation of HFD-induced lipotoxicity and hepatic steatosis, which were accompanied by the inhibition of autophagy and ER stress responses in the liver. In conclusion, despite the improvement of glucose tolerance, BJ supplementation promoted a major impact on lipid management mechanisms at liver and AT levels in prediabetic animals, which might affect disease course.
... Blueberries have demonstrated significant lipid-lowering and anti-obesity effects (Vendrame et al. 2014, Jiao et al. 2019. Jiao et al. (2019) reported significant decreases in TC and TG levels in the liver of HFD-fed rats, decreases in serum TG and LDL-c levels, and increase in HDL-C level following intervention with blueberry extract. ...
... Blueberry extract was reported to up-regulate genes which enhance fatty acid b-oxidation (PPARa and CPT1), while genes that enhance lipogenesis (PPARc, FAS and SREBP1) were down-regulated in the liver and white adipose tissue, thus indicative of a lipid-lowering effect (Wu et al. 2013, Jiao et al. 2019. Furthermore, blueberries down-regulated FAS and SREBP1 in the liver and abdominal adipose tissue of obese Zucker rats (Vendrame et al. 2014). In the above studies, anthocyanins were reported to play an integral role in the beneficial effects of the berries. ...
The global market for medicinal plants and herbs is on the increase due to their desirability, efficacy, and less adverse effects as complementary and alternative medications to the orthodox pharmaceuticals, perhaps due to their natural components and qualities. Metabolic syndromes are managed with changes in diet, exercise, lifestyle modifications and the use of pharmacological agents. Plants are now known to have potent antioxidant and cholinergic activities which are relevant to the management of several metabolic syndromes, which are unfortunately, co-morbidity factors in the coronavirus disease crisis. This review will focus on the biological activities of some plant products used as complementary and alternative medicines in the management of metabolic syndromes, and on their reported antiviral, antithrombotic, angiotensin-converting enzyme inhibitory properties, which are integral to their usage in the management of viral infections and may give an avenue for prophylactic and therapeutics especially in the absence of vaccines/formulated antiviral therapies.
... Diets enriched with blueberries have been reported to improve dyslipidemia. Plasma triglycerides (TG) and total cholesterol (TC) concentrations were significantly reduced in obese Zucker rats supplemented with 8% wild blueberry for 8 weeks [59] or 2% blueberry powder for 13 weeks compared to the control groups [28]. a reduction in serum TC and low density lipoprotein cholesterol (LDL-C) was observed, as well as in the levels of liver TG and TC following the consumption of blueberry juice. ...
... Antocyanins [30] Reduction of blood glucose levels; [29] Lowering of plasma TG, TC, and LDL-C concentrations [28,59,61] -Reduction in glucose, fasting insulin and insulin resistance [28] ...
Wild foods constitute an essential component of people's diets around the world. According to the Food and Agriculture Organization (FAO), over 100 million people in the EU consume wild foods, while 65 million collect some form of wild food themselves. The Mediterranean basin is a biodiversity hotspot of wild edible species. Nowadays, due to the renewed interest in alimurgic plants and the recent findings on the beneficial role of their phytochemical constituents, these species have been defined as "new functional foods". Research on natural products has recently regained importance with the growing understanding of their biological significance. Botanical food supplements marketed for weight and fat loss in obese subjects will be one of the most important items in marketed nutraceuticals. The aim of this report was to review the phytochemical compounds of Mediterranean wild edible species and their therapeutic potential against obesity and its related disorders. Results on the in vitro and in vivo activity of the most interesting plant extracts and their bioactive components are presented and discussed. The most interesting discoveries on their mechanisms of action are reported as well. Overall, this contribution highlights the importance and beneficial health roles of wild edible species.
... It has been reported that the anthocyanins might play a role in attenuating obesity by producing a decrease in weight and adipose tissue [4]. Controversial results were obtained in animals and human studies in obesity condition [5][6][7][8][9][10][11] by type of supplementation (fresh and/or commercial product or pure compound), dose, length of the study, and by different sizes and clinical characteristics of the enrolled sample. Furthermore, the pharmacological actions of anthocyanins could not be fully recognized without knowing the effects of treatment of anthocyanins alone, the effects of nonanthocyanin molecules, and the possible synergistic action between anthocyanins and the complex mixture of phytochemicals present in whole foods [12]. ...
... Seymour et al. [42] described that supplementation with 2% (wt/wt) blueberry powder (BBP) reduced the weight of intraperitoneal fat and enhanced the activity of the peroxisome proliferator-activated receptor (PPAR) in white adipose tissue (WAT) and skeletal muscle in Zucker-fatty rats [42]. Following the above mentioned studies, Vendrame et al. [43] reported that supplementation with 8% (wt/wt) wild blueberry powder (WBP) after 8 weeks of feeding significantly increased blood adiponectin levels as well as reduced the levels of inflammatory markers in WAT [43] and improved dyslipidemia [6]. However, WBP did not obtain reduced fasting blood glucose (FBG) and insulin levels in obese Zucker rats in this study [44]. ...
The obesity and its related comorbidities represent an emerging global health issue. The natural phytochemicals present in foods, including anthocyanins, might play role in attenuating obesity by producing a decrease in weight and adipose tissue. Nowadays it doesn’t exist a recommended daily allowance although a consumption between 250-400 mg/d, has been identified. This review focused on the current knowledge about anthocyanins’ role in obesity and its related comorbidities reported in animal models and humans. We summarized their target-identification and mechanism of action through several pathways and their final effects on health and well-being. Into consideration ongoing researches, we highlighted following key points:
-healthy relationship between anthocyanin supplementation and anti-obesity effects suffers of the same pros and cons evidenced when the beneficial responses to other phytochemical treatments towards different degenerative diseases have been considered; - the different dosage applied in animal versus clinical studies;
-the complex metabolism and biotransformation to which anthocyanins and phytochemicals are subjected in the intestine and tissues; -the possibility that different components present in the supplemented mixtures can interact generating antagonistic, synergistic or additive effects difficult to predict, -the difference between prevention and therapy. The evolution of the filed must seriously consider the need to establish new and adequate cellular and animal models which may, in turns, allow the design of more efficient and prevention targeted clinical studies.
... In addition, there is some evidence that blueberries might modulate lipid metabolism and improve dyslipidemia. Vendrame et al. (2014) reported that blueberry supplementation s ignificantly reduced plasma total cholesterol and TAG in obese Zucker rats, in addition to increasing expression of PPAR, PPARγ, and ATP-binding cassette transporter 1 in abdominal adipose tissue (AAT), and decreasing expression of fatty acid synthase and SREBP-1 in the liver and in AAT (Vendrame et al., 2014). ...
... In addition, there is some evidence that blueberries might modulate lipid metabolism and improve dyslipidemia. Vendrame et al. (2014) reported that blueberry supplementation s ignificantly reduced plasma total cholesterol and TAG in obese Zucker rats, in addition to increasing expression of PPAR, PPARγ, and ATP-binding cassette transporter 1 in abdominal adipose tissue (AAT), and decreasing expression of fatty acid synthase and SREBP-1 in the liver and in AAT (Vendrame et al., 2014). ...
This chapter presents recent evidence to demonstrate that different anthocyanin (ANC) aglycones can differ markedly in terms of bioavailability, absorption, metabolism, metabolic breakdown products, and excretion to produce wide-ranging impacts on human metabolic health and disease. In more recent years, stable isotope labeling has provided new insights into the complex issue of ANCs disposition after ingestion. ANC deposition in various tissues has been studied in animal models. Several studies have demonstrated that detectable levels of ANCs occur in brain tissue after ingestion. Modern nutritional supplementation with ANCs aimed at metabolic health promotion and disease risk reduction revealed several nutrigenomic biomarkers that might explain how an anthocyanin-rich diet influences gene transcription, protein expression, and metabolism. Taken together, these new findings provide a strong scientific basis for developing new anthocyanin-rich foods, cultivars of existing crops, and dietary supplements adapted to the specific needs of consumers and targeted to a specific group of metabolic risk factors.
... 2998 photodiode array detector (Waters). The separation was carried out by a C 18 ...
Increasing evidence links the impairment of intestinal permeability (IP), a feature of the intestinal barrier, to numerous dysmetabolic and dysfunctional conditions. Several host and environmental factors, including dietary factors, can negatively and/or positively affect IP. In this regard, polyphenol-rich foods including berries have been proposed as potential IP modulators. However, the exact mechanisms involved are not yet fully elucidated. The aim of the present study was to evaluate the effect of a wild blueberry (WB; V. angustifolium) powder, naturally rich in polyphenols, to affect Caco-2 cell monolayer permeability and to identify the potential mechanisms in modulating the IP process. Caco-2 cells were incubated with TNF-α (10 ng mL-1), as a pro-inflammatory stimulus, and supplemented for 24 hours with different concentrations (1 and 5 mg mL-1) of WB powder. The integrity of the intestinal cell monolayer was evaluated by measuring the transepithelial electrical resistance (TEER) and the paracellular transport of FITC-dextran. In addition, the production of the tight junction proteins, such as claudin-1 and occludin, as well as protein carbonyl and 8-hydroxy 2 deoxyguanosine, as oxidative stress markers, were quantified in the supernatant by ELISA kits. Overall, the treatment with WB powder (5 mg mL-1) mitigated the loss of Caco-2 cell barrier integrity, as documented by an increase in TEER and a reduction in FITC values. This modulation was accompanied by an upregulation of claudin-1 and a reduction of 8-OHdG. Conversely, no effect was documented for the lower concentration (1 mg mL-1) and the other IP markers, as well as oxidative stress markers analysed. In conclusion, our findings suggest a potential role of WB in the modulation of cell barrier integrity. This modulation process could be attributed to an increase in claudin-1 expression and a reduction in 8-OHdG. Further studies should be performed to corroborate the results obtained. In addition, since the effects were observed at doses of WB achievable with the diet, these findings should be substantiated also through in vivo approaches.
... Contradictory results from different studies due to differences in study design, sample size, and the participants' genetic characteristics. The results from some studies suggest that the mTOR inhibitory effect of anthocyanins through the activation of AMPK causes modulation of lipid metabolism and fat deposition in the liver (Lee et al., 2010;Vendrame et al., 2014). ...
Abstract Consumption of phytochemical‐rich foods relates to the prevention of chronic diseases. In this study we assessed the dietary phytochemical index (PI) in metabolic parameters, liver enzymes, and severity of fibrosis among nonalcoholic fatty liver disease patients. This cross‐sectional study was conducted on 210 patients with NAFLD. Fibrosis‐4 index (FLB4), nonalcoholic fatty liver disease fibrosis score (NFS), FBS, lipids profile, AST, ALT, ALP, and GGT were measured. PI was calculated through the information obtained from a validated semi‐quantitative food frequency. Multiple regression models were used to estimate mean difference changes in the evaluated variables associated with various dietary PI. Participants' mean ± SD of age and BMI were 39.23 ± 10.52 and 24.40 ± 2.64, respectively. We found that DPI is inversely associated with serum TG, TC, and LDL‐C and directly associated with serum HDL‐C and a higher score in DPI is associated with lower scores in NFS and FIB‐4. Multivariate linear regression showed that there is an inverse association between DPI and AST, ALT, ALP, GGT, NFS, and FIB‐4. Higher dietary PI could impact on reduction of NAFLD progression and improvement of metabolic parameters.
... Interestingly, even though different genes were up-or down-regulated by each berrybased beverage, the three beverages exerted a similar reduction effect on the accumulation of lipid vacuoles within the hepatocytes. Similar results were reported with the supplementation of wild blueberry fruits, which up-regulated the expression of the peroxisome proliferator-activated receptor-alpha (PPAR-α) in obese rats, which regulates the expression of Cpt1a and down-regulated the expression of the sterol regulatory element-binding protein 1 (SREBP-1), which regulates the expression of Fasn and Acaca genes [25]. On the other hand, the effect of strawberry fruit or derived products has not been reported on hepatic lipid metabolism. ...
There is an increasing interest in developing natural herb-infused functional beverages with health benefits; therefore, in this study, we aimed to evaluate the effect of strawberry, blueberry, and strawberry-blueberry blend decoction-based functional beverages on obesity-related metabolic alterations in high-fat and high-fructose diet-fed rats. The administration of the three berry-based beverages for eighteen weeks prevented the development of hypertriglyceridemia in obese rats (1.29–1.78-fold) and hepatic triglyceride accumulation (1.38–1.61-fold), preventing the development of hepatic steatosis. Furthermore, all beverages significantly down-regulated Fasn hepatic expression, whereas the strawberry beverage showed the greatest down-regulation of Acaca, involved in fatty acid de novo synthesis. Moreover, the strawberry beverage showed the most significant up-regulation of hepatic Cpt1 and Acadm (fatty acid β-oxidation). In contrast, the blueberry beverage showed the most significant down-regulation of hepatic Fatp5 and Cd36 (fatty acid intracellular transport). Nevertheless, no beneficial effect was observed on biometric measurements, adipose tissue composition, and insulin resistance. On the other hand, several urolithins and their derivatives, and other urinary polyphenol metabolites were identified after the strawberry-based beverages supplementation. In contrast, enterolactone was found significantly increase after the intake of blueberry-based beverages. These results demonstrate that functional beverages elaborated with berry fruits prevent diet-induced hypertriglyceridemia and hepatic steatosis by modulating critical genes involved in fatty acid hepatic metabolism.
... Recent evidence suggests that C. mas with its fruits and leaves are a good source of antioxidants due to its abundant content of anthocyanins, flavonoids, and other phenolics, iridoids, and vitamins [15][16][17]. C. mas have therapeutic effects on various diseases such as diabetes, microbial infections, oxidative stress, hyperlipidemia, and obesity [18][19][20][21][22]. There are also several reports confirming the hepatoprotective effects of C. mas in rats by reducing oxidative stress [23,24]. ...
... Green and red lines stand for increasing or decreasing metabolite blood levels between pre-and post-supplementation states within individual paired samples. Orn ornithine, DG diacylglycerol, Cer ceramide, Ind-SO4 indoxyl sulfate, TG triglyceride, HipAcid hippuric acid alone or mixed with other berries on weight management [42][43][44], markers of glucose/insulin resistance or sensitivity [10,[42][43][44][45][46], lipid profile [42,47,48], vascular health [49,50], kidney function [51] or inflammatory markers [10,[42][43][44][50][51][52][53]. Results from studies assessing other MetS phenotype parameters have been consistent with our findings overall. ...
Background
Blueberries contain high levels of polyphenolic compounds with high in vitro antioxidant capacities. Their consumption has been associated with improved vascular and metabolic health.
Purpose
The objective was to examine the effects of blueberry supplement consumption on metabolic syndrome (MetS) parameters and potential underlying mechanisms of action.
Methods
A randomized double-blind placebo-controlled intervention trial was conducted in adults at risk of developing MetS. Participants consumed 50 g daily of either a freeze-dried highbush blueberry powder (BBP) or a placebo powder for 8 weeks ( n = 49). MetS phenotypes were assessed at weeks 0, 4 and 8. Fasting blood gene expression profiles and plasma metabolomic profiles were examined at baseline and week 8 to assess metabolic changes occurring in response to the BBP. A per-protocol analysis was used.
Results
A significant treatment effect was observed for plasma triglyceride levels that was no longer significant after further adjustments for age, sex, BMI and baseline values. In addition, the treatment*time interactions were non-significant therefore suggesting that compared with the placebo, BBP had no statistically significant effect on body weight, blood pressure, fasting plasma lipid, insulin and glucose levels, insulin resistance (or sensitivity) or glycated hemoglobin concentrations. There were significant changes in the expression of 49 genes and in the abundance of 35 metabolites following BBP consumption. Differentially regulated genes were clustered in immune-related pathways.
Conclusion
An 8-week BBP intervention did not significantly improve traditional markers of cardiometabolic health in adults at risk of developing MetS. However, changes in gene expression and metabolite abundance suggest that clinically significant cardiometabolic changes could take longer than 8 weeks to present and/or could result from whole blueberry consumption or a higher dosage. BBP may also have an effect on factors such as immunity even within a shorter 8-week timeframe.
Clinical trial registration
clinicaltrials.gov, NCT03266055 , 2017
... In general, controversial results were obtained in animal and human studies of obesity by type of supplementation, dose, length of the study, and different sizes and clinical characteristics of the enrolled sample. Furthermore, since the studies used mostly plant extracts, the pharmacological actions of anthocyanins cannot be fully recognized without knowing the effects of treatment of anthocyanins alone, the effects of non-anthocyanin molecules, and the possible synergistic action between anthocyanins and the complex mixture of phytochemicals present in whole foods [119][120][121][122][123]. ...
Background
Obesity is a disease characterized by excessive accumulation of body fat, weight gain, increased glycemia and lipid profile. These alterations produce deleterious health effects through time. Faced with the growing search for coadjuvant options for obesity and its associated comorbidities, bioactive compounds such as flavonoids are an interesting alternative, since the beneficial effects of flavonoids on lipid levels, energy metabolism, and weight status have already been reported in the literature. This study was carried out to review the effect of some flavonoids tested in preclinical models of obesity.
Methods
We conducted a database search including MEDLINE (via PubMed), SCOPUS, EMBASE, LILACS and SCIELO and selected articles published until August 2020, using keywords related to flavonoids, obesity and animal experimentation and their MeSH variations.
Results
Forty-seven studies were selected. We noted that oral supplementation in the diet of flavonoids for a few weeks was able to reduce body weight, blood glucose, glucose tolerance, resistance to insulin, and fat and lipid profiles. These beneficial effects were related to antioxidant and anti-inflammatory actions by modulating different pathways, such as PPARγ, JNK and AMPK.
Conclusion
These findings strongly indicate the flavonoids quercetin, genistein, naringenin, apigenin, epigallocatechin gallate and cyanidin 3-glucoside have potential in complementary therapy against obesity.
... The reduction of SREBP-1 and SREBP-2 was also reported in mulberry water extract treated against oleic acid-induced HepG2 cells (Chang et al., 2013). Blue honeysuckle, H. sabdariffa, and wild blueberry were also reported to downregulate SREBP1c expression in HFD-fed mice (Villalpando-Arteaga et al., 2013;Vendrame et al., 2014;Kim et al., 2018;Chun et al., 2018). In addition, blueberry juice alone or in combination with Bifidobacteria also demonstrated a modulatory effect on SREBP1c expression ( Fig. 5; Ren et al., 2014). ...
Nonalcoholic fatty liver disease (NAFLD) refers to a metabolic syndrome linked with type 2 diabetes mellitus, obesity, and cardiovascular diseases. It is characterized by the accumulation of triglycerides in the hepatocytes in the absence of alcohol consumption. The prevalence of NAFLD has abruptly increased worldwide, with no effective treatment yet available. Anthocyanins (ACNs) belong to the flavonoid subclass of polyphenols, are commonly present in various edible plants, and possess a broad array of health-promoting properties. ACNs have been shown to have strong potential to combat NAFLD. We critically assessed the literature regarding the pharmacological mechanisms and biopharmaceutical features of the action of ACNs on NAFLD in humans and animal models. We found that ACNs ameliorate NAFLD by improving lipid and glucose metabolism, increasing antioxidant and anti-inflammatory activities, and regulating gut microbiota dysbiosis. In conclusion, ACNs have strong potential to attenuate NAFLD. However, further mechanistic studies are required to confirm these beneficial impacts of ACNs on NAFLD.
... In obese Zucker rats (OZR), 8% wild blueberry (WB) powder improved inflammation, lipid metabolism, and endothelial function after 8 weeks of treatment [85][86][87]. With an emphasis on glucose metabolism, a follow-up study fed OZR the same 8% WB diet for 8 weeks and measured fasting glucose, insulin, glycated hemoglobin, RBP4, and resistin, as well as gene expression of GLUT4, resistin, and RBP4 in both liver and adipose tissues [88]. ...
Obesity and type-2 diabetes trends continue to worsen in the United States. Dietary anthocyanins (typically provided by berries and other fruits) are reported to have protective effects against both conditions using a variety of experimental research models including animal and human feeding studies. This review highlights studies that explore the biochemical pathways in both tissue and rodent models which could explain clinical improvements noted with anthocyanin consumption. First, the primary mode of intestinal absorption of anthocyanins is through both sGLT1 and GLUT2 glucose transporters. Stronger binding affinities may allow anthocyanins to be more inhibitive to glucose absorption compared to the reverse, where GLUT2 expression may also be affected. Genetic or chemical inhibition of sGLT1 or GLUT2 demonstrate their essential function in anthocyanin absorption across the enterocyte, where the former interacts with a greater variety of anthocyanins but the latter is the major transporter for specific anthocyanin-glycosides. Once absorbed, anthocyanins positively modulate GLUT4 density and function in both skeletal muscle and adipose tissues via the upregulation of AMPK and restoration of insulin sensitivity. Antioxidant properties and phosphodiesterase inhibition by anthocyanins promote both mitochondrial function and density which could be novel targets for dietary management of obesity and its complications.
... In fact, experimental data arising from cell-free systems, standard cell-cultures, and/or isolated organelles highlight BB phytochemicals' ability to modulate non-redox mechanisms through their interactions with functionally diverse cellular targets, such as intercalation with DNA, transcription of several genes associated with key cellular functions, mitochondria dynamics, and even gut microbiota (GM) homeostasis [4,[15][16][17][18]. Convergent results are also reported in preclinical animal studies that emphasize BB consumption benefits in a panoply of chronic disorders paralleling obesity-related metabolic diseases such as cardiovascular disease (CVD), metabolic syndrome (MS) or type 2 diabetes mellitus (T2DM) [13,[19][20][21][22][23][24][25]. Interestingly, the association between human BB consumption and biomarker-based evidence of reduced risk of diseases has been also emphasized [13,[26][27][28][29][30]. ...
An emergent trend of blueberries' (BB) "prophylactic" consumption, due to their phytochemicals' richness and well-known health-promoting claims, is widely scaled-up. However, the benefits arising from BB indiscriminate intake remains puzzling based on incongruent preclinical and human data. To provide a more in-depth elucidation and support towards a healthier and safer consumption, we conducted a translation-minded experimental study in healthy Wistar rats that consumed BB in a juice form (25 g/kg body weight (BW)/day; 14 weeks' protocol). Particular attention was paid to the physiological adaptations succeeding in the gut and liver tissues regarding the acknowledged BB-induced metabolic benefits. Systemically, BB boosted serum antioxidant activity and repressed the circulating levels of 3-hydroxybutyrate (3-HB) ketone bodies and 3-HB/acetoacetate Pharmaceutics 2020, 12, 1094 2 of 29 ratio. Moreover, BB elicited increased fecal succinic acid levels without major changes on gut microbiota (GM) composition and gut ultra-structural organization. Remarkably, an accentuated hepatic mitochondrial bioenergetic challenge, ensuing metabolic transcriptomic reprogramming along with a concerted anti-inflammatory pre-conditioning, was clearly detected upon long-term consumption of BB phytochemicals. Altogether, the results disclosed herein portray a quiescent mitochondrial-related metabolomics and hint for a unified adaptive response to this nutritional challenge. The beneficial or noxious consequences arising from this dietary trend should be carefully interpreted and necessarily claims future research.
... In contrast to ndings made in human interventions, numerous animal studies reported bene ts of blueberries alone or mixed with other berries on weight management (42)(43)(44), markers of glucose/insulin resistance or sensitivity (10,(42)(43)(44)(45)(46), lipid pro le (42,47,48), vascular health (49,50), kidney function (51) or in ammatory markers (10,(42)(43)(44)(50)(51)(52)(53). Results from studies assessing other MetS phenotype parameters have been consistent with our ndings overall. ...
Background: Blueberries contain high level of polyphenolic compounds with high in vitro antioxidant capacities. Their consumption has been associated with improved vascular and metabolic health.
Purpose: The objective was to examine the effects of blueberry supplement consumption on metabolic syndrome (MetS) parameters and potential underlying mechanisms of action.
Methods: A randomized double-blind placebo-controlled intervention trial was conducted in adults at risk of developing MetS. Participants consumed 50g daily of either a freeze-dried highbush blueberry powder (BBP) or a placebo powder for 8 weeks (n=49). MetS phenotypes were assessed at week 0, 4 and 8. Fasting blood gene expression profiles and plasma metabolomic profiles were examined at baseline and week 8 to assess metabolic changes occurring in response to the BBP. A per-protocol analysis was used.
Results: Interaction effects were non-significant demonstrating that compared to the placebo, BBP had no statistically significant effect on body weight, blood pressure, fasting plasma lipid, insulin and glucose levels, insulin resistance (or sensitivity) and on glycated hemoglobin concentrations. However, there were significant within- and between-group differences including increased insulin resistance in the placebo group only, greater TG at week 4 in the BBP compared to placebo group and increased fasting insulin from week 4 to 8 in both groups. Moreover, there were significant changes in the expression of 49 genes and 35 metabolites following BBP consumption. Differentially regulated genes were clustered in immune-related pathways.
Conclusion: An 8-week BBP intervention did not significantly improve traditional markers of cardiometabolic health in adults at risk of developing MetS. However, metabolically relevant changes in gene expression and metabolites suggest that clinically significant cardiometabolic changes could take longer than 8 weeks to present and/or could result from whole blueberry consumption or a higher dosage. BBP may also have an effect on factors such as immunity even within a shorter 8-week timeframe.
Clinical trial registration: clinicaltrials.gov, NCT03266055, 2017, https://clinicaltrials.gov/ct2/show/NCT03266055?term=blueberry+vohl&draw=2&rank=1
... As observed previously, iron storage and absorption increased in the liver of NASH patients (21), and serum ALT levels decreased in subjects treated by bloodletting (22). Hence, dropped iron absorption by catechins, in particular EGCG, can be an efficacious limiting cure in NAFLD patients. ...
... However, no change was observed in HDL cholesterol concentration. This lipid profile induced by the wild blueberry ingestion suggests their role in the prevention of atherosclerosis [197]. Using a similar experimental design, a wild blueberry-enriched diet resulted in an MCP-1 concentration reduction in the perivascular adipose tissue of OZR, which also highlights their protective role regarding atherosclerosis [198]. ...
Anthocyanins are a class of water-soluble flavonoids widely present in fruits and vegetables. Dietary sources of anthocyanins include red and purple berries, grapes, apples, plums, cabbage, or foods containing high levels of natural colorants. Cyanidin, delphinidin, malvidin, peonidin, petunidin, and pelargonidin are the six common anthocyanidins. Following consumption, anthocyanin, absorption occurs along the gastrointestinal tract, the distal lower bowel being the place where most of the absorption and metabolism occurs. In the intestine, anthocyanins first undergo extensive microbial catabolism followed by absorption and human phase II metabolism. This produces hybrid microbial–human metabolites which are absorbed and subsequently increase the bioavailability of anthocyanins. Health benefits of anthocyanins have been widely described, especially in the prevention of diseases associated with oxidative stress, such as cardiovascular and neurodegenerative diseases. Furthermore, recent evidence suggests that health-promoting effects attributed to anthocyanins may also be related to modulation of gut microbiota. In this paper we attempt to provide a comprehensive view of the state-of-the-art literature on anthocyanins, summarizing recent findings on their chemistry, biosynthesis, nutritional value and on their effects on human health.
... In vitro studies show that anthocyanins, such as cyanidin 3-glucoside, may inhibit lipogenesis, promote lipolysis, and decrease steatosis by activating the AMPK pathway (39). Also, blueberry consumption stimulates liver peroxisome proliferator-activated receptor-α activity and decreases hepatic lipid accumulation in obese Zucker rats (40). In the current study, participants who consumed freeze-dried blueberries compared with those who consumed placebo had lower triglyceride concentrations and better glycemic control. ...
Background:
Blueberries are dietary sources of polyphenols, specifically anthocyanins. Anthocyanins have been identified as having a strong association with type 2 diabetes risk reduction; however, to date few human clinical trials have evaluated the potential beneficial health effects of blueberries in populations with type 2 diabetes.
Objectives:
We investigated the effects of blueberry consumption for 8 wk on cardiometabolic parameters in men with type 2 diabetes.
Methods:
In a double-blind, parallel-arm, randomized controlled trial, 52 men who are US veterans [mean baseline characteristics: age, 67 y (range: 51-75 y); weight, 102 kg (range: 80-130 kg); BMI (in kg/m2), 34 (range: 26-45)] were randomly assigned to 1 of 2 intervention groups. The interventions were either 22 g freeze-dried blueberries or 22 g placebo. The study participants were asked to consume 11 g freeze-dried blueberries or placebo with each of their morning and evening meals along with their typical diet.
Results:
Mean ± SE hemoglobin A1c (7.1% ± 0.1% compared with 7.5% ± 0.2%; P = 0.03), fructosamine (275.5 ± 4.1 compared with 292.4 ± 7.9 µmol/L; P = 0.04), triglycerides (179.6 ± 10.1 compared with 199.6 ± 19.9 mg/dL; P = 0.03), aspartate transaminase (23.2 ± 1.4 compared with 30.5 ± 2.7 units/L; P = 0.02), and alanine transaminase (35.6 ± 1.5 compared with 48.3 ± 2.9 units/L; P = 0.0003) were significantly lower for those consuming blueberries for 8 wk than for those consuming the placebo. Fasting plasma glucose concentrations; serum insulin, total cholesterol, LDL-cholesterol, HDL-cholesterol, and C-reactive protein concentrations; blood pressure; and body weight were not significantly different after 8 wk consumption of blueberries compared with the placebo.
Conclusions:
Consumption of 22 g freeze-dried blueberries for 8 wk may beneficially affect cardiometabolic health parameters in men with type 2 diabetes.This trial was registered at clinicaltrials.gov as NCT02972996.
... It has been shown that PPARα knockout (/) mice developed severe hepatic steatosis upon fasting as a result of failure to up regulate the fatty acid oxidation pathway [35]. Our result confirmed that the therapeutic effect of ERAbE and quercetin on lipid metabolism in HepG2 induced fatty liver cells could be partly due to PPARα up regulation (inducing lipolysis) and SREBP1c down regulation (reducing lipogenesis) [36,37]. ...
Nonalcoholic Fatty Liver Disease (NAFLD) is characterized by the excessive triglycerides accumulation as lipid droplets in the cytoplasm of hepatocytes, which result from an imbalance between uptake, synthesis, export, and oxidation of fatty acids. In this study, we have evaluated the effect of a natural extracts from mushroom (Agaricus bisporus) enriched in the antioxidant ergothioneine, on the reduction of lipid accumulation in HepG2 cells. Ergothioneine Rich A. bisporus Extracts (ERAbE) decreased the intracellular concentration of lipids, lipids droplets size and intracellular TG content through down regulation of SREBP1c, PPARγ and ACAT1 together with PPARα up regulation. These extracts also down regulated hepatic lipogenesis through SREBP1c activation. Moreover, increased lipolysis was found to be induced through PPARα.
Therefore, we concluded that EEAbE has the ability to reduce significantly the intracellular lipid content in an in vitro model induced by oleic acid. EEAbE down regulated SREBP1c expression, leading to an inhibition of hepatic lipogenesis. The activation of PPARα induced lipolysis being responsible for lowering hepatic fat content together with the reduction of lipogenesis. EEAbE has a regulatory effect on lipid accumulation in HepG2 cells.
... Moreover, it has also been reported to help prevent obesity and certain gastrointestinal disorders, such as duodenal ulcer, constipation and hemorrhoids (Anderson et al. 2009, Eswaran, Muir, and Chey 2013, Fuller et al. 2016, Kaczmarczyk, Miller, and Freund 2012, Slavin 2013, Wu et al. 2015. A concrete example of this biological potential is blueberry, as this fruit has been associated with many health benefits, with existing works reporting on its antioxidant, antimicrobial, antitumoral and antiinflammatory activity, as well as gut modulating capacity (Br€ anning et al. 2009, Carey, Gomes, and Shukitt-Hale 2014, Dulebohn et al. 2008, Guglielmetti et al. 2013, Molan et al. 2009, Neto 2007, Piljac-Zegarac, Bel s cak, and Piljac 2009, Silva et al. 2016, Jo et al. 2015, Vendrame et al. 2014, Taverniti et al. 2014, Ren, Huang, and Cheng 2014. ...
With the increase in evidences directly linking diet and health, several foodstuffs, such as phenolic rich fruits and vegetables, have emerged as possessing potential health benefits. Plants, given their fiber and phenolic content (and their intrinsic biological potential), have long been considered as contributing to health promotion. Therefore, the present work aimed to review the existing evidences regarding the various potential benefits of plant extracts’ and plant extract-based products’ consumption, with emphasis on in vivo works and epidemiological studies whenever available. Overall, the information available supports that, while there are indications of the potential benefits of plant extracts’ consumption, further human-based studies are still needed to establish a true cause-effect.
... Seymour et al. (2011),Vendrame et al. (2013) andVendrame, Daugherty, et al. (2014) reported that the supplementation of a high-fat diet with blueberry powder led to ...
With the strengthening of the link between diet and health, several foodstuffs have emerged as possessing potential health benefits such as phenolic rich fruits and vegetables. Blueberries, along with other berries, given their flavonoid and antioxidant content have long since been considered as a particularly interesting health promoting fruit. Therefore, the present work aimed to compile the existing evidences regarding the various potential benefits of blueberry and blueberry based products consumption, giving particular relevance to in vivo works and epidemiological studies whenever available. Overall, the results demonstrate that, while the evidences that support a beneficial role of blueberry and blueberry extracts consumption, further human based studies are still needed.
... Intake of blueberry leaf extract reduced body weight (20%) and improved insulin resistance as well as prevent obesity in mice with a high-fat diet [70], however blueberry extract possess a therapeutic tool against comorbidities related with obesity [71]. Expression of fatty acid synthase was significantly decreased in the adipose tissue of the liver and abdomen when wild blueberry consumption was increased [72]. Obesity and diabetes are becoming a global health problem; however, freeze-dried blueberry powder can treat and prevent obesity-related chronic diseases [73]. ...
Functional ingredients in blueberry have the best health benefits. To obtain a better understanding of the health role of blueberry in chronic disease, we conducted systematic preventive strategies for functional ingredients in blueberry, based on comprehensive databases, especially PubMed, ISI Web of Science, and CNKI for the period 2008–2018. Blueberry is rich in flavonoids (mainly anthocyanidins), polyphenols (procyanidin), phenolic acids, pyruvic acid, chlorogenic acid, and others, which have anticancer, anti-obesity, prevent degenerative diseases, anti-inflammation, protective properties for vision and liver, prevent heart diseases, antidiabetes, improve brain function, protective lung properties, strong bones, enhance immunity, prevent cardiovascular diseases, and improve cognitive decline. The anthocyanins and polyphenols in blueberry are major functional ingredients for preventive chronic disease. These results support findings that blueberry may be one of the best functional fruits, and further reveals the mechanisms of anthocyanins and polyphenols in the health role of blueberry for chronic disease. This paper may be used as scientific evidence for developing functional foods, nutraceuticals, and novel drugs of blueberry for preventive chronic diseases.
... In abdominal adipose tissue, wild berry consumption resulted in the increasing of the expression of transcription factors PPARc and PPARa in the obese Zucker rats, while down-regulating the lipid synthesis protein sterol regulatory element-binding protein 1 (SREBP-1). ATP-binding cassette transporter 1 was increased in the abdominal adipose tissue following wild berry consumption (Vendrame, Daugherty, Kristo et al. 2014). However, the effect of anthocyanins on PPARc in vitro is incompatible to the in vivo studies. ...
Metabolic syndrome develops to several related chronic diseases, such as obesity, cardiovascular disease, hypertension, diabetes, fatty liver disease. Diseases are outcomes of various cells dysfunction, which are especially acting with a network in metabolic syndrome. Anthocyanins are natural edible pigments widely existed in dark-colored fruits, vegetables, and grains. Epidemiological investigation and nutritional intervention of anthocyanins have exhibited broad-spectrum biological effects that benefit patients with metabolic syndrome related chronic diseases. Whereas the underlying mechanisms and the effects of anthocyanins on critical cells in chronic metabolic diseases are complex and elusive. Therefore, this review summarizes the studies about the effects of anthocyanins on various metabolism related chronic diseases, and mainly focuses on the effects and underlying molecular mechanisms on critical cells. We confirmed that anthocyanins are efficient on adipocytes, endothelial cells, inflammatory cells, hepatocytes, intestinal cells and gut microbiota, but lack of evidence on platelets, skeletal muscle cells, hepatic stellate cells and pancreatic beta cells. Additionally, we discussed the structure-function relationship of anthocyanins and the metabolites. This review summarizes the development of studies on anthocyanins with its target cells in metabolic syndrome, and discusses the unclear aspects of the anthocyanins research work, which is necessary for the future clinical application.
... Parallel studies in high-fat fed obesity-prone Zucker rats found that red raspberry supplementation reduced fasting blood triglycerides (Kirakosyan et al., 2016), while wild blueberry supplementation (Vaccinium angustifolium) also significantly reduced plasma triglycerides and total cholesterol with no significant effect on HDL-C levels (Vendrame et al., 2014). While some studies indicate that berry-rich diets had the potential to modulate lipoprotein and triglyceride profile in severely dyslipidaemic rodent models, variable responses were observed. ...
Historically, the consumption of berries has been associated with a variety of health benefits. Many traditional or folk medicines have used berries in remedies for a range of health issues. In addition, substantial scientific evidence has accrued over the past 20 years, highlighting that components from berries have measurable beneficial effects on health. Berries are best known for their accumulation of antioxidant components (mainly associated with polyphenols, carotenoids, and vitamin C) and have amongst the highest antioxidant capacity of commonly eaten foods; however, recent evidence also suggests that a wider variety of phytochemical components present in berries may also contribute towards beneficial effects on health. This article provides an overview of current scientific evidence derived from animal, human, and epidemiologic studies regarding the effects of consuming berries or important phytochemical components of berries on various neurodegenerative and non‐communicable diseases and discusses the underlying mechanisms involved.
... 40 Our result confirmed that the therapeutic effect of quercetin on lipid metabolism in Huh7.5-induced fatty liver cells is partly due to PPARα upregulation (inducing lipolysis) and SREBP-1c downregulation (reducing lipogenesis). 41,42 Cynara scolymus extract increased PPARα gene expression levels in the model of steatosis which controls fatty acid degradation. Anderson, et al. showed that pathogenesis of NASH increased the pool of free fatty acids through de novo lipid synthesis and nuclear receptors activation (SREBP-1, ChREBP-1, and PPARγ). ...
Material and methods:
Huh7.5 cells were exposed to oleic acid (OA) and treated with quercetin and extracts to observe the lipid accumulation, the intracellular-TG concentration and the LD size. Sterol regulatory element binding proteins-1 (SREBP-1), peroxisome proliferator-activated receptor (PPARα-γ) and cholesterol acyltransferase (ACAT) gene expression levels were analysed.
Results:
Quercetin decreased the intracellular lipids, LD size and the levels of intracellular-TG through the down-regulation of SREBP-1c, PPARγ and ACAT1 increasing PPARα. The natural-extracts suppressed OA-induced lipid accumulation and the intracellular-TG. They down-regulate the hepatic lipogenesis through SREBP-1c, besides the activation of lipolysis through the increasing of PPARα expression.
Conclusions:
Quercetin and the aqueous extracts decrease intracellular lipid accumulation by down-regulation of lipogenesis and up-regulation of lipolysis.
... [4] The myocardial ischemia leads to the development of arrhythmias and necrosis of the myocardium. [5] The oxidative stress due to free radicals generation and apoptotic damage are major factors in myocardium ischemia which plays an important role in the development of ischemic heart diseases such as MI. A variety of qualitative and quantitative changes in the myocardium takes place due to the myocardial damage. ...
Objectives:
To investigate the effect of coenzyme Q10 (CoQ10) on apoptotic myocardial cell death in rat model of heart ischemia and reperfusion I/R injury.
Materials and methods:
Eighteen rats (200-250 g) were divided into three groups of 6 rats in each. Group I (sham-operated control group): this is the control group. The animals received the surgical procedure without IR injury or any drug treatment. Group II (I/R group): ischemia was accomplished by the occlusion of coronary artery for 30 min followed by reperfusion for 45 min and Group-III (Coenzyme Q10 treated group): Treated with CoQ10 at a dose of 1 mg/kg, postoperative for 7 days before induction of IR injury.
Results:
The study revealed that pretreatment with CoQ10 has shown protective effect on apoptotic rat heart and agreed with earlier reports that CoQ10 significantly protects from oxidative stress and cytopathological changes caused by cardiac ischemia followed by reperfusion and attenuated decrease of antioxidant enzymes. Nitric oxide production in the heart of ischemic rats was significantly increased by the pretreatment with CoQ10 in comparison with IR group.
Conclusions:
CoQ10 protects against cardiac apoptosis induced by IR injury by significantly decreasing the apoptotic DNA and regulating the expression of Bcl-2 gene.
... Numerous studies demonstrate that Cy-3-G has beneficial effects on human health. Most studies have evaluated the effects of anthocyanins on lipid metabolism and found that anthocyanins reduced lipid accumulation by breaking the balance of lipogenesis and lipolysis (Vendrame, Daugherty, Kristo, & Klimis-Zacas, 2014). In addition, anthocyanins could improve insulin resistance (Takikawa et al., 2010), which may be a potential therapy for diabetes. ...
Cyanidin-3-O-β-glucoside (Cy-3-G) has protective properties in many diseases. Whether Cy-3-G has protective effects on alcohol induced liver injuries remains uncertain. In our study, mice were fed with a high fat high cholesterol diet (HFC) plus ethanol for 12 weeks. Cy-3-G supplementation reversed the liver damage induced by alcohol. In vitro studies, Cy-3-G restored the intracellular energy status of LX-2 cells and inhibited the activation of LX-2 cells induced by ethanol plus palmitate. The protective effect of Cy-3-G is via the increase of AMPK phosphorylation and autophagy. In conclusion, Cy-3-G ameliorated chronic alcoholic liver injuries, possibly by improving energy metabolic status. Specifically, liver fibrosis was protected by Cy-3-G via inhibiting the activation of stellate cells, which was mediated partially by AMPK/autophagy signaling pathway.
... Adiponectin also lowers muscle triglyceride levels by increasing the influx and combustion of free fatty acids resulting in decreased hepatic level of triglycerides [65]. It has recently been reported that a diet supplemented with wild blueberry powder significantly increased blood adiponectin levels and decreased inflammatory marker levels in the white adipose tissue [94], including those related to cardiovascular risk (C-reactive protein (CRP), interleukins, TNFa, and Vascular cell adhesion protein 1 (VCAM-1)) [95]; decreased NF-jB activity [96] and serum LPS levels [97]; and ameliorated dyslipidemia [98], showing the anti-inflammatory effects of the different ACNs present in the fruit [31]. ...
Obesity is characterized by low-grade inflammation and a number of metabolic disorders. Distal gut microbes' content (microbiota) is not yet fully understood but evidence shows that it is influenced by internal and external factors that modulate its composition and function. The evidence that gut microbiota composition can differ between healthy and obese individuals, as well as for those who maintain specific dietary habits, has led to the study of this environmental factor as a key link between the pathophysiology of obesity and gut microbiota. Data obtained about the role of anthocyanins (ACNs) in microbiota may lead to different strategies to manipulate bacterial populations and promote health. Anthocyanins have been identified as modulators of gut microbiota that contribute to obesity control and these bioactive compounds should be considered to have a prebiotic action. This review addresses the relevance of knowledge about the influence of anthocyanins-rich food consumption on microbiota, and their health-promoting potential in the pathophysiology of obesity. © 2017 BioFactors, 2017.
... Most hepatotoxic chemicals damage hepatic cells by producing ROS/RNS. Many anthocyanins have been studied for their role in the modulation of lipid metabolism and fat deposition in different tissues, including the liver [85]. An fractioned anthocyanin (AF) obtained from purple-fleshed sweet potato was shown to have hepatoprotective activity in acetaminophen-induced liver damage in mice by preventing paracetamol (APAP) caused hepatic glutathione (GSH) and hepatic GSH levels depletion [86]. ...
Anthocyanins, a flavonoid class of polyphenols, are water soluble dark colored natural pigments found
in fruits and vegetables. Owing to their wide distribution in plant materials, dietary consumption of anthocyanins
is high compared to other flavonoids. Anthocyanins, due to their multifaceted medicinal properties are the active
components in many herbal folk medicines. As in vitro and in vivo results, animal models, and clinical trials in
various cell lines suggest, anthocyanins possess antioxidant, antidiabetic, antihyperlipidemic, anti-inflammatory,
anticarcinogenic, antiulcer, and preventive activities against cardiovascular diseases. Additionally, anthocyanins
exhibit chemotherapeutic, cardioprotective, hepatoprotective, and neuroprotective activities. In the diet, anthocyanins
are absorbed in the stomach and intestinal cells and rapidly detected in the plasma. These promising
properties of anthocyanins may well provide health benefits against chronic diseases.
... Anthocyanins, such as cyanidin-3-O-glucoside, in vitro regulate the expression and activity of key enzymes involved in lipid metabolism including LPL, fatty acid synthase and ABCA1. These findings might explain the observed effects of blueberry consumption on the lipid profile [49]. Phenolic acids and flavonoids are also important phytochemical classes in MetS treatment. ...
The aim of this study was to investigate the effect of blueberry (Vaccinium virgatum) fruit extract on metabolic, behavioral and oxidative stress parameters in the hippocampus and cerebral cortex of mice submitted to an experimental model of metabolic syndrome induced by a highly palatable diet (HPD). Mice C57BL/6 were divided into 4 experimental groups: (1) received standard chow and saline orally, (2) received standard chow and blueberry hydroalcoholic extract, (3) received HPD and saline orally, (4) received HPD and blueberry hydroalcoholic extract. The animals were treated for 150days. Our results showed that the animals fed with HPD presented insulin resistance, increased body weight, visceral fat, glucose, triglycerides, and total cholesterol when compared to the control group. The blueberry extract prevented the increase of these metabolic parameters. Also, the extract was able to reduce the levels of thiobarbituric acid reactive substances in the cerebral cortex and hippocampus of animals submitted to HPD. In contrast, no differences were observed in the total thiol content, activity of the antioxidant enzymes catalase and superoxide dismutase. In addition, the HPD fed animals showed a significant increase in immobility time in the forced swimming test and blueberry prevented this alteration, although no changes were observed in the ambulatory behavior, as well as in the anxiolytic profile of these animals. Overall, our findings suggest that chronic consumption of blueberry extract exhibits hypoglycemic, hypolipidemic, antidepressant-like and antiperoxidative effects in an animal model of metabolic syndrome.
Plants are an untapped natural resource; their secondary metabolites take part in a variety of pharmacological activities, making them an essential ingredient in the synthesis of novel medications and the source of reserve resources in this process. Hepatitis and liver cancer are two conditions that can result from non-alcoholic fatty liver disease (NAFLD). NAFLD is a condition that now affects a significant section of the global population. There is a need for preventative action on predisposing factors. Due to their effectiveness and few side effects, herbal medications are frequently utilized for the prevention and treatment of NAFLD. This review discusses the pathogenetic processes of NAFLD and the evidence brought to support the potential of botanical species and their derivatives in limiting the causes that predispose to the onset of NAFLD.
Cardiovascular diseases (CVDs) are among the leading causes of morbidity and mortality worldwide. Unhealthy dietary habits have clearly been shown to contribute to the development of CVDs. Beyond the primary nutrients, a healthy diet is also rich in plant-derived compounds. Natural polyphenols, found in fruits, vegetables, and red wine, have a clear role in improving cardiovascular health. In this review, we strive to summarize the results of the relevant pre-clinical and clinical trials that focused on some of the most important natural polyphenols, such as resveratrol and relevant flavonoids. In addition, we aim to identify their common sources, biosynthesis, and describe their mechanism of action including their regulatory effect on signal transduction pathways. Finally, we provide scientific evidence regarding the cardiovascular benefits of moderate, long-term red wine consumption.
This study investigated the effect of FBP (fermented blueberry pomace by the mixture of Lactobacillus rhamnosus GG and Lactobacillus plantarum-1) on hyperlipidemia in high-fat diet (HFD)-induced C57BL/6J obese mice. The results indicated that FBP significantly reduced the weight gain, liver and fat indexes, and hyperlipidemia of HFD mice. Serum TC, TG, and LDL-C in HFD mice were significantly decreased through supplementation with FBP, and serum SOD, GSH-Px, CAT, and T-AOC in H-FBP group were increased by 28.25%, 26.84%, 23.30%, and 19.79%, respectively. Furthermore, FBP reduced the activity of ALT, AST, and LPS; down-regulated the expression of inflammation-related cytokines (TNF-α, IL-1β, and IL-6); and improved lipid metabolism by up-regulating PPAR-α and down-regulating SREBP-1 and FAS. Thus, FBP alleviated obesity, liver injury, and inflammation caused by a HFD by increasing antioxidant capacity and reducing leptin production, indicating that FBP is a nutrient-rich beverage with the potential to relieve obesity. Generally, this study highlights a new use of blueberry pomace.
Metabolic syndrome (MetS) is major public health concern. Diet can play a major role in the prevention and/or progression of the MetS. At 8 weeks of age, male obese Zucker rat (OZR) and their lean littermates (LZR) were placed on a control or an 8% w/w whole red raspberry (WRR)-enriched diet for 8 weeks. Circulating levels of inflammatory cytokines and their gene expression in the liver and adipose tissue were evaluated. Several lipid markers were measured in the plasma, liver and adipose tissue. The expression of eight genes related to lipid metabolism were evaluated, both in liver and adipose tissue. Phenylephrine (Phe)-induced vasoconstriction and acetylcholine (Ach)-induced vasorelaxation were measured in aortic rings in the presence or absence of L-N-monomethyl-arginine (L-NMMA) and mefenamic acid (MFA). Prostanoid levels were measured in the aortic effluent. Vascular function related gene were analyzed in the aorta. Plasma levels of interleukin-6 (IL-6) decreased in the OZR consuming a WRR diet compared to the OZR-C (p
Metabolic syndrome (MetS) is a collection of metabolic risk factors associated with an increased risk of developing atherosclerosis. Reducing levels of modifiable atherogenic risk factors is an essential goal in the prevention of atherosclerosis. Since there is an established relationship between metabolic syndrome, oxidative stress, chronic inflammation and cardiovascular disease, the first study focused on demonstrating these links. Therefore, this research focuses on a sedentary population who work under conditions that predispose them to risk factors of metabolic syndrome and who are likely to develop atherosclerosis ultimately. Accordingly, a comprehensive evaluation of metabolic syndrome risk factors was conducted on 79 transport drivers. The clinical examination collected anthropometric data and blood biochemistry results. Daily step counts calculated by the Fitbit over seven days were also used to monitor their activity trends over time. Health assessments were conducted at the beginning of the study. The results showed that 68% (n = 51) of participants were recorded as having three or more risk factors which can contribute to MetS including obesity, hyperglycaemia, lipid profile abnormalities, blood pressure, hyperuricemia and markers of inflammation. This study also demonstrated that there are interconnections between oxidative stress and chronic inflammation with MetS components highlighting the role of oxidative stress and inflammation in metabolic syndrome and atherosclerosis. It could be suggested that the potential use of anthocyanins as antioxidants and with anti-inflammatory properties as an alternative approach for the prevention and management of atherosclerosis in MetS population. Initially, the use of an in vitro model of endothelial cells can offer valuable mechanistic insights into the development and progression of inflammatory conditions that provide an efficient platform for product screening before conducting a human intervention trial.
Based on findings from the literature review, it is hypothesised that anthocyanin might exert protective effects on healthy human aortic endothelial cells against inflammation and oxidative stress in vitro. The second study aimed to examine and compare the abilities of healthy and diabetic human aortic endothelial cells to incorporate anthocyanins’ potential benefits against hydrogen peroxide (H2O2) as an oxidative stressor and lipopolysaccharide (LPS) to induce inflammation. Cultured Primary Human Aortic Endothelial Cells (HAEC) and Diseased-(type II diabetic) Aortic Endothelial Cells (D-HAEC) were exposed to oxidative stress by H2O2 (75 μM) and LPS (1μg/ml) and
were treated with the anthocyanin (AC, 50 μl/ml). The results showed that anthocyanins might be responsible for protecting that aortic endothelial cells against inflammatory insult. These findings may have important implications for preserving endothelial cell function and preventing the initiation of endothelial cell damage that leads to platelets activation and coagulation associated with endothelial dysfunction.
Finally, based on the in vitro finding, the last chapter aimed to investigate the antithrombotic effects of same berry-derived anthocyanin supplements on biomarkers of atherosclerosis, platelet function, and the expression of pro-atherogenic genes in a population with metabolic syndrome. A total of 55 participants in two groups of Normal and MetS (age 25-75y) were given 320 mg anthocyanin supplements twice daily for four weeks in a clinical trial. The effects of berry-derived supplementation were examined on features of metabolic syndrome, including fasting blood glucose, lipid profile, inflammatory markers, oxidative stress marker (uric acid), platelet surface markers, and the expression of pro-atherogenic genes. The results showed that anthocyanin consumption for four weeks significantly decreased the average fasting blood glucose (FBG) level by 13.3 % in the MetS group. Similarly, significant reductions were observed in triglyceride (24.9%) and low-density lipoprotein (LDL) (33.1%) levels in the MetS group compared with the Normal group (P ≤ 0.05). Anthocyanin supplementation also caused a reduction (18%) in high sensitivity C-reactive protein (hs-CRP), an inflammatory biomarker, with no significant difference in the Normal group. There was a positive correlation between decreased hs-CRP values and the levels of LDL-C and FBG in the MetS group (P ≤ 0.05). Anthocyanin supplements also decreased ADP-induced platelet activation configuration expressed as P-selectin by 40%. The data here revealed that anthocyanin intake showed an inhibitory effect on the gene expression of proinflammatory cytokines, including interleukin (IL)-1A, tumour necrosis factor-alpha (TNF-α) and interleukin (IL)-6, as well as endothelial cell adhesion molecule-1 (ECAM-1) and cyclooxygenase (COX)-2, with stimulatory effects on the expression of superoxide dismutase (SOD) and Peroxisome proliferator-activated receptor gamma (PPRAG). Thus, these findings suggest that short-term consumption of anthocyanin supplements may have atheroprotective effects through the inhibition of chronic inflammation and platelet activation and improvement of MetS components.
Non-alcoholic fatty liver disease is a major risk factor of the metabolic syndrome (MetS). The effect of whole red raspberry (WRR) consumption on lipid metabolism was investigated in the obese Zucker rat (OZR), a model for the MetS. Male OZRs (n = 16) and their lean littermates (lean Zucker rat) (n = 16) at 8 weeks of age were placed on a control or an 8% WRR-enriched diet for 8 weeks. Plasma triglycerides (TGs), total cholesterol, high-density lipoprotein cholesterol (HDL-C), and non-HDL-C levels, and hepatic concentration of TG were measured. The expression of nine genes related to lipid metabolism was evaluated, both in liver and adipose tissue. A WRR-enriched diet reduced plasma cholesterol and HDL-C and increased plasma TG, while it decreased hepatic TG accumulation in the OZR. The OZR assigned to a WRR exhibited upregulation of microsomal triglyceride transfer protein (Mttp) and downregulation of fatty acid synthase (Fas) expression in the liver. Results showed a decrease in accumulation of liver TG and gene expression modulation of enzymes and transcription factors associated with lipid metabolism, suggesting a possible hepatoprotective role of a WRR-enriched diet.
This study appears to be the first attempt to use a novel microencapsulated apricot kernel powder (MAKP) to improve diabetes-and obesity-related parameters in the serum and liver tissue of normal-diet-and cafeteria-diet-fed rats. For this purpose, bitter apricot kernel powder (AKP) was microencapsulated within a maltodextrin matrix under optimized conditions, and the effects of treatment with MAKP at two doses (4 and 8 mg) on the parameters in normal-diet-and cafeteria-diet-fed rats were established. MAKP was characterized in terms of its molecular properties, revealing that AKP could be successfully encapsulated. MAKP was established to have clear effects of increasing (P < 0.01) the levels of the native thiol, total thiol, total antioxidant status, high-density lipoprotein and thioredoxin reductase parameters and of decreasing (P < 0.01) the levels of the total oxidant status, disulfide, indexes I and II, oxidative stress index, total cholesterol, low-density lipoprotein, glucose, triglyceride, catalase, superoxide dismutase, tumor necrosis factor alpha and glutathione peroxidase parameters. However, these effects were dose independent and more prominent in the rats fed cafeteria diet. As a consequence, the use of MAKP significantly (P < 0.01) improved these parameters in the rats fed cafeteria diet, suggesting that the use of MAKP may contribute to the current efforts that are being exerted to treat diabetes and obesity-related disorders.
Le diabète de type 2 (DT2) représente l’un des principaux défis de santé du XXI ème siècle. En 2015, 415 millions de personnes dans le monde étaient touchées tandis que 318 millions de plus présentaient un prédiabète, un stade défini comme à haut risque de développer la pathologie, mais encore réversible. Les recommandations hygiéno-diététiques (activité physique et alimentation) constituent la première ligne d’intervention dans le cadre de la lutte contre l’apparition du diabète de type 2. L’objectif de cette thèse était d'évaluer l’effet de deux stratégies interventionnelles inscrites dans les mesures hygiéno-diététiques sur le développement du DT2. L’étude 1 visait à comparer l’effet de deux modalités d’exercice chronique (continu à intensité modérée vs. intermittent de haute intensité) sur le développement du DT2 de jeunes souris db/db. L’étude 2 s’attachait à mesurer les effets d’un mélange de 5 extraits de plantes (Composition brevetée Totum-63,) sur le développement du DT2 à partir de deux modèles du prédiabète : la jeune souris db/db et la souris rendue insulinorésistante suite à un régime riche en graisses. Dans la 1 ère étude, l’entrainement intermittent de haute intensité a amélioré le contrôle glycémique indépendamment d’une adaptation de la fonction mitochondriale via notamment une augmentation du contenu musculaire en Glut4. Dans notre seconde étude, Totum- 63 a entrainé une amélioration du contrôle glycémique et de la sensibilité à l’insuline dans nos deux modèles. Plusieurs mécanismes sur différents tissus impliqués dans la physiopathologie du DT2 ont été mis en évidence, suggérant une action pléiotrope de Totum-63. En conclusion, ces résultats soutiennent l’intérêt de ces deux approches non-médicamenteuses dans le cadre de la lutte contre le développement du DT2. L’étude de l’action de l’activité physique combinée à celle de Totum-63, présente un intérêt supplémentaire et constitue un prolongement possible des travaux de cette thèse.
Metabolic syndrome (MetS) is a global challenge for atherosclerosis. It was hypothesized that a four-week consumption of anthocyanin supplements by the MetS patients who had three or more risk factors linked with metabolic syndrome would have a greater improvement in cardiometabolic biomarkers,and would also reduce the risk of thrombosis. A total of 55 participants in two groups of Normal healthy and MetS (age 25-75y) were given 320 mg anthocyanin supplements twice daily for four weeks. Platelet coagulant activities, lipid profiles, fasting blood glucose, inflammatory and oxidative stress biomarkers were measured before and after supplementation to evaluate the atheroprotective effects of anthocyanins in the study subjects. Four weeks anthocyanin supplementation significantly decreased cardiometabolic risk factors including the average serum fasting blood glucose (FBG) (by 13.3%, P < .05) and lipid profiles by significant reduction in triglyceride (by 24.9%, P < .05) and LDL-C (by 33.1%, P < .05) in the MetS group. Anthocyanin supplementation also decreased high sensitivity C-reactive protein (hs-CRP) level (by 28%, P < .05) in females. However, no significant differences in serum UA (uric acid) and HDL-C were observed between anthocyanin pre- and post-treatment in both groups. Moreover, Anthocyanin supplements decreased ADP-induced platelet activation configuration expressed as P-selectin by 40% (P < .05). There was a positive correlation between decreased hs-CRP values and the levels of LDL-C and FBG in the MetS group (P < .05). These results support the hypothesis that anthocyanin supplementation exerts anti-atherogenicity effects by improving cardiometabolic risk factors and reducing thrombogenicity in the MetS population.
An increasing number of studies indicate that dietary polyphenols are beneficial to non-alcoholic fatty liver (NAFL) disease. However, the published reports about marine polyphenols are still limited. In this work, the ameliorative effect of polyphenols from Laminaria (L.) japonica on NAFL was investigated in vivo. According to the spectral analyses, dieckol was identified from L. japonica. After NAFL was induced by a high-fat diet, the ICR mice were administered dieckol-enriched extract (DEE) (50 mg/kg/day) for 4 weeks. Compared with the normal diet (ND) group, significant (P < 0.05) improvements in body weight gain, liver index, visceral fat index, plasma lipid profiles, and hepatic fat deposition were observed in ND + DEE group. Moreover, DEE supplementation selectively ameliorated levels of phosphorylated-AMP-activated protein kinase, carnitine palmitoyltransferase-1, and peroxisome proliferator-activated receptor-α in liver. Therefore, polyphenols from L. japonica might have potential ameliorative effect on hepatic steatosis via stimulating hepatic fatty acid β-oxidation.
Bilberries and blueberries are represented by various species of the genus Vaccinum in the plant family of Ericaceae. Powered by their polyphenol composition which is largely dominated by anthocyanins, the numerous health benefits of these fruits including for treating type 2 diabetes (T2D) and associated diseases have been advocated in recent years. This chapter examines, the botany, chemistry, pharmacokinetics profile and pharmacology of these plants. From the color of the fruits to the biologically active principles, the chemistry of bilberries and blueberries that attribute to hypoglycemic, antiobesity and lipid lowering effects are presented. In vitro, animal models and human clinical trials that relate to their health benefits in diabetes pathologies including hypertension and retinopathy are scrutinized. As with the mechanistic-based lines of evidences in favor of their health claims, controversies that arose from numerous experimental variables are discussed.
The berry consumption have been associated with cardiovascular disease prevention in recent years. Atherosclerosis is one of the major causes of cardiovascular diseases. However, research on the prevention of atherosclerosis through consuming individual whole berries, specifically direct evidence, remains scarce. Therefore, further elucidating the role berries play in the prevention of atherosclerosis is warranted. In this perspective paper, blueberries were selected to articulate research strategies for studying athero-protective effects of berries. Studies from human subjects and various animal models are summarized. The mechanisms by which blueberries may act, through reducing oxidative stress, decreasing inflammation, improving endothelial dysfunction, regulating cholesterol accumulation and trafficking, along with potentially influencing gut microbiota, are also discussed. Blueberries contain high levels of polyphenolic compounds, which were widely indicated as major bioactive compounds. Nonetheless, the metabolites/catabolites after blueberry consumption, such as simple phenolic acids, rather than original compounds in berries, may be the actual in vivo bioactive compounds. Future research should focus on obtaining more direct evidence, preferably in humans, understanding of the mechanisms of action at the molecular level, and identifying bioactive compounds as well as which compounds act synergistically to convey health benefits. The research strategy discussed here may also be applied to the studies of other fruits and berries.
Purpose: The objective of the present study was to determine whether fermentation can increase the protective effects of blueberry liquid in a high-fat diet-induced obese mice model. Methods: Male C57BL/6J mice were fed a high-fat diet (HD, 60% fat, w/w,), HD supplemented with 10 ml/kg BW/day of blueberry liquid (BHD, blueberry high-fat diet), or HD supplemented with 10 ml/kg BW/day of fermented blueberry liquid (FBHD, fermented blueberry high-fat diet) for 10 weeks. Results: There were significant decreases in the body, epididymal adipose tissue, and liver weights of blueberry-fed groups compared to HD, whereas there were no significant differences in food intake among the groups. Furthermore, blueberry liquid groups, especially fermented blueberry liquid, significantly attenuated the contents of hepatic triglycerides and total cholesterol induced by HD. Serum LDL-cholesterol was significantly lower in the BHD and FBHD-fed groups, whereas FBHD significantly increased the serum HDL-cholesterol level compared to the control. Concentrations of aspartate transaminase, alanine transaminase, and leptins in serum were also reduced by blueberry liquid supplementation. The mRNA expression of hepatic acetyl CoA carboxylase was significantly reduced in both the BHD and FBHD groups compared to HD. Furthermore, FBHD altered the mRNA expression level of hepatic lipolysis genes. Conclusion: In conclusion, these results suggest that blueberry, especially fermented blueberry liquid, may improve obesity-related abnormalities.
Não existe consenso sobre a estratégia nutricional mais adequada para tratar a Síndrome Metabólica (SM), de tal forma que ocorra redução do risco cardiovascular. O presente estudo foi desenhado para avaliar a força de evidência dos benefícios de diferentes intervenções nutricionais na remissão da SM. A busca virtual foi realizada nas bases de dados Medline, Cochrane Library e PubMed, de ensaios clínicos randomizados publicados no período entre 1999 a 2009, em qualquer língua, em indivíduos com 18 anos ou mais e diagnóstico de SM, independente do critério. O operador booleano and foi utilizado na combinação dos MeSH terms "Metabolic Syndrome", "Síndrome x Metabólica" e "Metabolic Syndrome X"; dos entry terms "Dysmetabolic Syndrome X", Metabolic Cardiovascular Syndrome", "Metabolic X Syndrome", "Syndrome X, Metabolic" adicionados dos termos "diet", "intervention and diet", "treatment and diet" e "supplementation". Para cada estudo incluído na revisão foi estimada a Prevalência de SM e o Cálculo da Eficácia após o período de seguimento. Medidas de risco relativo para cada estudo foram descritas pelo Forest Plot. Foram identificados 131 artigos, os quais após critérios de elegibilidade resultaram em 15 estudos. Estes foram separados em quatro grupos: dieta normocalórica associada a exercícios; dieta normocalórica isolada; dieta hipocalórica associada a exercícios; e dieta hipocalórica isolada. Os ensaios com dieta hipocalórica associada à prática de exercícios apresentaram valores mais elevados de eficácia, colaborando para ressaltar os aspectos globais da mudança do estilo de vida no tratamento da SM, onde a alimentação saudável e reduzida em calorias deve ser complementada com a prática de atividade física.
There is no consensus on the most appropriate nutritional strategy for treating metabolic syndrome (MS), such that cardiovascular risk is reduced. This study was designed to assess the strength of evidence of the benefits of various nutritional interventions in MS remission. Performed in Medline, Cochrane Library and PubMed databases, the virtual search consisted of randomized clinical trials published between 1999 and 2009 in any language, studies involving individuals aged 18 or older and diagnosed with MS, regardless of the criterion. The Boolean operator and was used in the combination of the MeSH terms "Metabolic Syndrome", "Metabolic x Syndrome" and "Metabolic Syndrome X", the entry terms "Dysmetabolic Syndrome X", Metabolic Cardiovascular Syndrome," "Metabolic X Syndrome" and "Syndrome X, Metabolic", plus the terms "diet", "intervention and diet", "treatment and diet" and "supplementation". For each study included in the review, we estimated the prevalence of MS and the calculation of effectiveness after the follow-up period. Relative risk measures for each study were described by Forest Plot. We identified 131 articles, which, after eligibility criteria, resulted in 15 studies. These studies were divided into four groups: normocaloric diet associated with exercise; isolated normocaloric diet, low-calorie diet combined with exercises; and isolated low-calorie diet. Tests with low-calorie diet associated with exercising revealed higher efficiency values, helping to emphasize the global aspects of lifestyle change in the treatment of MS, in which healthy and low-calorie diet should be complemented with the practice of physical activity.
Metabolic syndrome can precede the development of type 2 diabetes and cardiovascular disease and includes phenotypes such as obesity, systemic inflammation, insulin resistance, and hyperlipidemia. A recent epidemiological study indicated that blueberry intake reduced cardiovascular mortality in humans, but the possible genetic mechanisms of this effect are unknown. Blueberries are a rich source of anthocyanins, and anthocyanins can alter the activity of peroxisome proliferator-activated receptors (PPARs), which affect energy substrate metabolism. The effect of blueberry intake was assessed in obesity-prone rats. Zucker Fatty and Zucker Lean rats were fed a higher-fat diet (45% of kcal) or a lower-fat diet (10% of kcal) containing 2% (wt/wt) freeze-dried whole highbush blueberry powder or added sugars to match macronutrient and calorie content. In Zucker Fatty rats fed a high-fat diet, the addition of blueberry reduced triglycerides, fasting insulin, homeostasis model index of insulin resistance, and glucose area under the curve. Blueberry intake also reduced abdominal fat mass, increased adipose and skeletal muscle PPAR activity, and affected PPAR transcripts involved in fat oxidation and glucose uptake/oxidation. In Zucker Fatty rats fed a low-fat diet, the addition of blueberry also significantly reduced liver weight, body weight, and total fat mass. Finally, Zucker Lean rats fed blueberry had higher body weight and reduced triglycerides, but all other measures were unaffected. In conclusion, whole blueberry intake reduced phenotypes of metabolic syndrome in obesity-prone rats and affected PPAR gene transcripts in adipose and muscle tissue involved in fat and glucose metabolism.
Among all fruits, berries have shown substantial cardio-protective benefits due to their high polyphenol content. However, investigation of their efficacy in improving features of metabolic syndrome and related cardiovascular risk factors in obesity is limited. We examined the effects of blueberry supplementation on features of metabolic syndrome, lipid peroxidation, and inflammation in obese men and women. Forty-eight participants with metabolic syndrome [4 males and 44 females; BMI: 37.8 +/- 2.3 kg/m(2); age: 50.0 +/- 3.0 y (mean +/- SE)] consumed freeze-dried blueberry beverage (50 g freeze-dried blueberries, approximately 350 g fresh blueberries) or equivalent amounts of fluids (controls, 960 mL water) daily for 8 wk in a randomized controlled trial. Anthropometric and blood pressure measurements, assessment of dietary intakes, and fasting blood draws were conducted at screening and at wk 4 and 8 of the study. The decreases in systolic and diastolic blood pressures were greater in the blueberry-supplemented group (- 6 and - 4%, respectively) than in controls (- 1.5 and - 1.2%) (P lt 0.05), whereas the serum glucose concentration and lipid profiles were not affected. The decreases in plasma oxidized LDL and serum malondialdehyde and hydroxynonenal concentrations were greater in the blueberry group (- 28 and - 17%, respectively) than in the control group (- 9 and - 9%) (P lt 0.01). Our study shows blueberries may improve selected features of metabolic syndrome and related cardiovascular risk factors at dietary achievable doses.
In aged mice, the redox-regulated transcription factor nuclear factor-kappaB (NF-kappaB) becomes constitutively active in many tissues, as well as in cells of the hematopoietic system. This oxidative stress-induced activity promotes the production of a number of pro-inflammatory cytokines, which can contribute to the pathology of many disease states associated with aging. The administration to aged mice of agents capable of activating the alpha isoform of the peroxisome proliferator-activated receptor (PPARalpha) was found to restore the cellular redox balance, evidenced by a lowering of tissue lipid peroxidation, an elimination of constitutively active NF-kappaB, and a loss in spontaneous inflammatory cytokine production. Aged animals bearing a null mutation in PPARalpha failed to elicit these changes following treatment with PPARalpha activators, but remained responsive to vitamin E supplementation. Aged C57BL/6 mice were found to express reduced transcript levels of PPARalpha and the peroxisome-associated genes acyl-CoA oxidase and catalase. Supplementation of these aged mice with PPARalpha activators or with vitamin E caused elevations in these transcripts to levels seen in young animals. Our results suggest that PPARalpha and the genes under its control play a role in the evolution of oxidative stress excesses observed in aging.
ATP binding cassette transporter A1 (ABCA1) mediates the cellular efflux of phospholipids and cholesterol to lipid-poor apolipoprotein A1 (apoA1) and plays a significant role in high density lipoprotein (HDL) metabolism. ABCA1's role in the causation of Tangier disease, characterized by absent HDL and premature atherosclerosis, has implicated this transporter and its regulators liver-X-receptoralpha (LXRalpha) and peroxisome proliferator activated receptorgamma (PPARgamma) as new candidates potentially influencing the progression of atherosclerosis. In addition to lipid regulation, these genes are involved in apoptosis and inflammation, processes thought to be central to atherosclerotic plaque progression. A Medline-based review of the literature was carried out. Tangier disease and human heterozygotes with ABCA1 mutations provide good evidence that ABCA1 is a major candidate influencing atherosclerosis. Animal and in vitro experiments suggest that ABCA1 not only mediates cholesterol and phospholipid efflux, but is also involved in the regulation of apoptosis and inflammation. The complex and beneficial interactions between apoA1 and ABCA1 seem to be pivotal for cholesterol efflux. The expression of the ABCA1 is tightly regulated. Furthermore the plaque microenvironment could potentially promote ABCA1 protein degradation thus compromising cholesterol efflux. PPAR-LXR-ABCA1 interactions are integral to cholesterol homeostasis and these nuclear receptors have proven anti-inflammatory and anti-matrix metalloproteinase activity. Therapeutic manipulation of the ABCA1 transporter is feasible using PPAR and LXR agonists. PPAR agonists like glitazones and ABCA1 protein stabilization could potentially modify the clinical progression of atherosclerotic lesions.
It is widely accepted that stimulation of reverse cholesterol transport, the efflux of excess cholesterol from peripheral tissues and transferring it to the liver for biliary excretion, is becoming an important component in reducing excess cholesterol deposition in atherosclerotic plaques. The ATP-binding cassette transporter has been identified as a key regulator of macrophage cholesterol efflux and apoAI-mediated reverse cholesterol transport. In vivo studies have documented anthocyanins, a large group of naturally phenolic compounds rich in plants, possess substantial capacities in improving plasma cholesterol levels. In this study, we investigated the potential role of anthocyanins in modulating cholesterol efflux from mouse peritoneal macrophages and macrophage-derived foam cells and the possible molecular mechanism linking ABCA1 to cholesterol efflux. Incubation of the mouse peritoneal macrophages and macrophage-derived foam cells with cyanidin-3-O-beta-glucoside and peonidin-3-O-beta-glucoside led to dose-dependent (1-100 microM) induction in cholesterol efflux and ABCA1 mRNA expression, and this effect could be blocked by the ABCA1 inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, disodium salt, and a general inhibitor of gene transcription actinomycin D. Treatment of the macrophages with anthocyanins also activated peroxisome proliferator-activated receptor gamma, liver X receptor alpha mRNA expression, and their mediated gene expression. Addition of geranylgeranyl pyrophosphate ammonium salt or GW9662 markedly inhibited the anthocyanin-induced increase of ABCA1 gene expression and apoAI-mediated cholesterol efflux. These data demonstrated that anthocyanin induces cholesterol efflux from mouse peritoneal macrophages and macrophage-derived foam cells and that stimulation of cholesterol efflux by anthocyanin is mediated, at least in part, by peroxisome proliferator-activated receptor gamma-liver X receptor alpha-ABCA1 signaling pathway activation.
The increased prevalence of obesity in Western society has been well established for many years, and with this trend, the prevalence of other associated pathologies including insulin resistance, dyslipidaemia, hypertension and the genesis of a proinflammatory and prothrombotic environment within individuals is also rapidly increasing, resulting in a condition known as the~metabolic syndrome. From a physiological perspective, one of the most severe consequences of the metabolic syndrome is a progressive inability of the cardiovascular system to adequately perfuse tissues and organs during either elevated metabolic demand and, if sufficiently severe, under basal levels of demand. For the study of the metabolic syndrome, the OZR (obese Zucker rat) represents an important tool in this effort, as the metabolic syndrome in these animals results from a chronic hyperphagia, and thus can be an excellent representation of the human condition. As in afflicted humans, OZR experience an attenuated functional and reactive hyperaemia, and can ultimately experience an ischaemic condition in their skeletal muscles at rest. The source of this progressive ischaemia appears to lie at multiple sites, as endothelium-dependent vasodilator responses are strongly impaired in OZR, and specific constrictor processes (e.g. adrenergic tone) may be enhanced. Whilst these active processes may contribute to a reduction in blood flow under resting conditions or with mild elevations in metabolic demand, an evolving structural alteration to individual microvessels (reduced distensibility) and microvascular networks (reduced microvessel density) also develop and may act to constrain perfusion at higher levels of metabolic demand. Given that constrained muscle perfusion in the metabolic syndrome appears to reflect a highly integrated, multi-faceted effect in OZR, and probably in humans as well, therapeutic interventions must be designed to address each of these contributing elements.
As new drugs are developed, it is essential to appropriately translate the drug dosage from one animal species to another. A misunderstanding appears to exist regarding the appropriate method for allometric dose translations, especially when starting new animal or clinical studies. The need for education regarding appropriate translation is evident from the media response regarding some recent studies where authors have shown that resveratrol, a compound found in grapes and red wine, improves the health and life span of mice. Immediately after the online publication of these papers, the scientific community and popular press voiced concerns regarding the relevance of the dose of resveratrol used by the authors. The animal dose should not be extrapolated to a human equivalent dose (HED) by a simple conversion based on body weight, as was reported. For the more appropriate conversion of drug doses from animal studies to human studies, we suggest using the body surface area (BSA) normalization method. BSA correlates well across several mammalian species with several parameters of biology, including oxygen utilization, caloric expenditure, basal metabolism, blood volume, circulating plasma proteins, and renal function. We advocate the use of BSA as a factor when converting a dose for translation from animals to humans, especially for phase I and phase II clinical trials.
Two feeding trials were conducted with pigs to determine the effects of blueberry supplementation on plasma lipid levels and other indices of cardiovascular benefit. In the first trial, where basal diets contained a high level of plant-based components (70 % soya, oats and barley), supplementation with 1, 2 and 4 % blueberries resulted in a decrease in total, LDL- and HDL-cholesterol. The greatest reduction was observed in the 2 % blueberry-fed pigs, where total, LDL- and HDL-cholesterol were reduced 11.7, 15.1 and 8.3 %, respectively. In the second trial where basal diets contained only 20 % (w/w) of soya, oats and barley, the lipid-modulating effect of blueberries was attenuated, so that supplementation with 1.5 % blueberries reduced total cholesterol by 8 %, which occurred only in pigs whose diets had been supplemented with cholesterol (0.08 %), NaCl (0.11 %) and fructose (9 %). In the first feeding trial, blueberry supplementation had no effect on blood platelet activity. Blueberry supplementation also had no effect on the susceptibility of leucocyte DNA to oxidation in the first trial and no effect on the susceptibility of LDL to oxidation in the second trial. Results of these two feeding trials are discussed in relation to the effects of basal diet composition on lipid-modulating effects of blueberries.
Elevated plasma lipids, glucose, insulin, and fatty liver are among components of metabolic syndrome, a phenotypic pattern that typically precedes the development of Type 2 diabetes. Animal studies show that intake of anthocyanins reduces hyperlipidemia, obesity, and atherosclerosis and that anthocyanin-rich extracts may exert these effects in association with altered activity of tissue peroxisome proliferator-activated receptors (PPARs). However, studies are lacking to test this correlation using physiologically relevant, whole food sources of anthocyanins. Tart cherries are a rich source of anthocyanins, and whole cherry fruit intake may also affect hyperlipidemia and/or affect tissue PPARs. This hypothesis was tested in the Dahl Salt-Sensitive rat having insulin resistance and hyperlipidemia. For 90 days, Dahl rats were pair-fed AIN-76a-based diets supplemented with either 1% (wt:wt) freeze-dried whole tart cherry or with 0.85% additional carbohydrate to match macronutrient and calorie provision. After 90 days, the cherry-enriched diet was associated with reduced fasting blood glucose, hyperlipidemia, hyperinsulinemia, and reduced fatty liver. The cherry diet was also associated with significantly enhanced hepatic PPAR-alpha mRNA, enhanced hepatic PPAR-alpha target acyl-coenzyme A oxidase mRNA and activity, and increased plasma antioxidant capacity. In conclusion, physiologically relevant tart cherry consumption reduced several phenotypic risk factors that are associated with risk for metabolic syndrome and Type 2 diabetes. Tart cherries may represent a whole food research model of the health effects of anthocyanin-rich foods and may possess nutraceutical value against risk factors for metabolic syndrome and its clinical sequelae.
This study investigates the ability of a wild blueberry (WB)‐enriched diet to improve subclinical inflammatory status in the obese Zucker rat (OZR), an experimental model for the human metabolic syndrome. Twenty OZR and 20 lean controls (LZR) were fed either a control (C) or an 8% WB diet for 8 weeks. Blood levels of interleukin 6 (IL6), TNFα and adiponectin (APN) were significantly higher in OZR compared to LZR, independent of treatment. Within the OZR group, IL6 and TNFα were significantly lower in the WB group (219.3 ± 8.0 and 28.8 ± 0.8 pg/mL respectively) compared to controls (257.7 ± 7.7 and 38.7 ± 0.9 pg/mL), whereas APN levels were higher (20.7 ± 1.5 vs 17.0 ± 1.1 μg/mL). Expression of IL6, TNFα and NF‐kB was significantly lower in the WB group of OZR both in the liver (−65%, −59% and −25% respectively) and the abdominal adipose tissue (−64%, −52% and −65%). Furthermore, expression of these genes was markedly increased in OZR on C diet compared to their lean controls, and this effect was almost completely reversed by the WB treatment. Liver expression of C‐reactive protein significantly decreased in both groups following WB treatment (−16% in LZR and −25% in OZR). Expression of APN in the adipose tissue significantly increased following WB treatment in LZR (+25%), but not in OZR. In conclusion, results of this study suggest that WB consumption results in a markedly improved inflammatory status in the OZR.
Grant Funding Source : Maine Wild Blueberry Commission
The two most commonly used methods to analyze data from real-time, quantitative PCR experiments are absolute quantification and relative quantification. Absolute quantification determines the input copy number, usually by relating the PCR signal to a standard curve. Relative quantification relates the PCR signal of the target transcript in a treatment group to that of another sample such as an untreated control. The 2(-DeltaDeltaCr) method is a convenient way to analyze the relative changes in gene expression from real-time quantitative PCR experiments. The purpose of this report is to present the derivation, assumptions, and applications of the 2(-DeltaDeltaCr) method. In addition, we present the derivation and applications of two variations of the 2(-DeltaDeltaCr) method that may be useful in the analysis of real-time, quantitative PCR data. (C) 2001 Elsevier science.
Publisher Summary This chapter discusses the analysis of total phenols and other oxidation substrates and antioxidants by means of Folin-Ciocalteu reagent. Analyses of the Folin-Ciocalteu (FC) type are convenient, simple, and require only common equipment and have produced a large body of comparable data. Under proper conditions, the assay is inclusive of monophenols and gives predictable reactions with the types of phenols found in nature. Because different phenols react to different degrees, expression of the results as a single number—such as milligrams per liter gallic acid equivalence—is necessarily arbitrary. Because the reaction is independent, quantitative, and predictable, analysis of a mixture of phenols can be recalculated in terms of any other standard. The assay measures all compounds readily oxidizable under the reaction conditions and its very inclusiveness allows certain substances to also react that are either not phenols or seldom thought of as phenols (e.g., proteins). Judicious use of the assay—with consideration of potential interferences in particular samples and prior study if necessary—can lead to very informative results. Aggregate analysis of this type is an important supplement to and often more informative than reems of data difficult to summarize from various techniques, such as high-performance liquid chromatography (HPLC) that separate a large number of individual compounds .The predictable reaction of components in a mixture makes it possible to determine a single reactant by other means and to calculate its contribution to the total FC phenol content. Relative insensitivity of the FC analysis to many adsorbents and precipitants makes differential assay—before and after several different treatments—informative.
Background and aim:
Atherosclerosis is a chronic inflammatory disease and previous studies have demonstrated that anthocyanin inhibits atherosclerosis. In the present study, we explored the effects of anthocyanins on inflammatory cytokines in hypercholesterolemic adults and cell lines.
Methods and results:
A total of 150 subjects with hypercholesterolemia consumed a purified anthocyanin mixture (320 mg/d) or a placebo twice a day for 24 weeks in a randomized, double-blind trial. Anthocyanin consumption significantly decreased the levels of serum high sensitivity C-reactive protein (hsCRP) (-21.6% vs. -2.5%, P = 0.001), soluble vascular cell adhesion molecule-1 (sVCAM-1) (-12.3% vs. 0.4%, P = 0.005) and plasma IL-1β (-12.8% vs. -1.3%, P = 0.019) compared to the placebo. We also found a significant difference in the LDL-cholesterol (-10.4% vs. 0.3%, P = 0.030) and HDL-cholesterol level changes (14.0% vs. -0.9%, P = 0.036) between the two groups. In cell culture assays in vitro, purified anthocyanin mixture, delphinidin-3-Ο-β-glucoside (Dp-3g) and cyanidin-3-Ο-β-glucoside (Cy-3g) inhibited IL-6 and IL-1β-induced CRP production (P < 0.05) in HepG2 cell line and LPS-induced VCAM-1 secretion (P < 0.05) in porcine iliac artery endothelial cell line respectively in a dose-dependent manner. In addition, the reduction of inflammatory cytokines associated with anthocyanin mixture was stronger when compared with the effects of Dp-3g and Cy-3g separately (P < 0.05).
Conclusions:
Anthocyanin mixture reduced the inflammatory response in hypercholesterolemic subjects. In addition, different anthocyanin compounds were found to have additive or synergistic effects in mediating anti-inflammatory responses in vitro cell culture assays.
Purpose:
Wild blueberries (WB) (Vaccinium angustifolium) are rich sources of polyphenols, such as flavonols, phenolic acids and anthocyanins (ACNs), reported to decrease the risk of cardiovascular and degenerative diseases. This study investigated the effect of regular consumption of a WB or a placebo (PL) drink on markers of oxidative stress, inflammation and endothelial function in subjects with risk factors for cardiovascular disease.
Methods:
Eighteen male volunteers (ages 47.8 ± 9.7 years; body mass index 24.8 ± 2.6 kg/m²) received according to a cross-over design, a WB (25 g freeze-dried powder, providing 375 mg of ACNs) or a PL drink for 6 weeks, spaced by a 6-week wash-out. Endogenous and oxidatively induced DNA damage in blood mononuclear cells, serum interleukin levels, reactive hyperemia index, nitric oxide, soluble vascular adhesion molecule concentration and other variables were analyzed.
Results:
Wild blueberry drink intake significantly reduced the levels of endogenously oxidized DNA bases (from 12.5 ± 5.6 % to 9.6 ± 3.5 %, p ≤ 0.01) and the levels of H₂O₂-induced DNA damage (from 45.8 ± 7.9 % to 37.2 ± 9.1 %, p ≤ 0.01), while no effect was found after the PL drink. No significant differences were detected for markers of endothelial function and the other variables under study.
Conclusions:
In conclusion, the consumption of the WB drink for 6 weeks significantly reduced the levels of oxidized DNA bases and increased the resistance to oxidatively induced DNA damage. Future studies should address in greater detail the role of WB in endothelial function.
Selected flavonoids (kaempferol, quercetin, myricetin) and phenolic acids (p-coumaric, caffeic, ferulic, p-hydroxybenzoic, gallic and ellagic acids) were simultaneously detected from 19 berries using a simple High Performance Liquid Chromatographic (HPLC) method. These phenolics have been proposed to have beneficial effects on health as antioxidants and anticarcinogens. Marked differences were observed in the phenolic profiles among the berries, with certain similarities within families and genera. The major phenolic compound analyzed in the genus Vaccinium was quercetin in lingonberry and cranberry, and its level was high also in blueberries and bilberry. In the genus Ribes, quercetin was the main compound in gooseberry, red currant and black currant. Ellagic acid was the main phenolic compound in the berries of the genus Rubus (red raspberry, Arctic bramble and cloudberry) and genus Fragaria (strawberry). Our data suggest that berries have potential as good dietary sources of quercetin or ellagic acid.
The collection of impaired glucose metabolism, central obesity, elevated blood pressure, and dyslipidemia is identified as metabolic syndrome (MetS). It is estimated that approximately 25% of the world's population has MetS. In the United States, MetS is more common in men and Hispanics, and its incidence increases with age. Metabolic syndrome increases the risk of developing cardiovascular disease and type 2 diabetes mellitus. The underlying risk factors include insulin resistance and abdominal obesity. Confusion about MetS exists in part due to the lack of a consensus definition and treatment protocol. Treatment of MetS begins with therapeutic lifestyle changes and then pharmacologic treatment of the syndrome's individual components. Effective interventions include diet modification, exercise, and use of pharmacologic agents to treat risk factors. Weight loss and increasing physical activity significantly improve all aspects of MetS. A diet that includes more fruits, vegetables, whole grains, monounsaturated fats, and low-fat dairy products will benefit most patients with MetS. Physicians can be most effective in advising patients by customizing specific lifestyle recommendations after assessing patients for the presence of risk factors.
Wild blueberries are a rich source of polyphenols and other compounds that are highly metabolized by the intestinal microbiota and may, at the same time, affect the intestinal environment itself. A repeated-measure, crossover dietary intervention on human volunteers was designed to study the effect of six week consumption of a wild blueberry ( Vaccinium angustifolium ) drink, versus a placebo drink, in modulating the intestinal microbiota. Relative to total eubacteria, Bifidobacterium spp. significantly increased following blueberry treatment (P ≤ 0.05), while Lactobacillus acidophilus increased after both treatments (P ≤ 0.05). No significant differences were observed for Bacteroides spp., Prevotella spp., Enterococcus spp., and Clostridium coccoides . Bifidobacteria, which have been largely proposed to be of benefit for the host, appeared to be selectively favored suggesting an important role for the polyphenols and fiber present in wild blueberries. Results obtained suggest that regular consumption of a wild blueberry drink can positively modulate the composition of the intestinal microbiota.
Cyanidin-3-O-β-glucoside (Cy-3-g)-rich foods have been reported to inhibit the onset of obesity, but whether the pure anthocyanin supplementation affects obesity remains uncertain.
Cy-3-g supplementation significantly reduced obesity, accumulation of fat in visceral adipose and liver tissues, and plasma triglyceride levels. Furthermore, adenosine monophosphate (AMP)-activated protein kinase phosphorylation (pAMPK) in the skeletal muscle and visceral adipose were significantly increased by Cy-3-g consumption. This was followed by the activation of lipoprotein lipase (LPL) in plasma and skeletal muscle but the suppression of this enzyme in visceral adipose. LPL activation in skeletal muscle cells and its suppression in adipocytes by Cy-3-g were blocked by inhibition of pAMPK.
Our present data thus demonstrate that Cy-3-g improves obesity and triglyceride metabolism in KK-Ay mice. The underlying mechanism is found to be partly related to the activation of LPL in plasma and skeletal muscle, and inhibition of LPL in adipose tissue following the activation of pAMPK.
The effect of a wild blueberry-enriched diet on vasoconstriction and vasorelaxation was examined in the adult, 20-week-old spontaneously hypertensive rat (SHR) after 8 weeks of a control (C) or an 8% wild blueberry (WB) diet. Nitric oxide (NO)- and cyclooxygenase (COX)-mediated aortic responses were examined ex vivo with the agonists L-phenylephrine (Phe) and acetylcholine (Ach), in the absence or presence of the NO synthase (NOS) inhibitor L-NG-monomethyl arginine (L-NMMA) or the COX inhibitor mefenamic acid (MFA). The vasoconstriction elicited by Phe was reduced in the WB group, attributed to the NO pathway, favoring a lower vascular tone under basal conditions. Acetylcholine-induced vasorelaxation in the WB group was possibly mediated through the COX, but not the NO pathway. These findings document the potential of wild blueberries to modify major pathways of vasomotor control and improve the vascular tone in the adult SHR with endothelial dysfunction.
The effect of wild blueberry consumption on anthocyanin (ACNs) distribution and metabolism in Sprague-Dawley (SD) rats was investigated. Thirty-two rats were fed for 4 or 8 weeks with a control (C) or a wild blueberry-enriched diet (8%) (WB). Anthocyanin profile in plasma, urine, feces, brain, and liver was evaluated by LC-MS/MS, and significantly increased in urine and not in feces after 8 weeks on the WB diet compared to that in 4 weeks, but no anthocyanins were detected in plasma, liver, and brain samples either in the C or WB groups. Metabolites of ACNs were detected in the plasma, urine, feces, and tissues of both the C and WB groups, but the urinary excretion of hippuric acid increased significantly after 4 and 8 weeks of WB consumption. Thus, it seems that ACNs are metabolized by the intestinal microflora to respective phenyl-alkyl acids, which can be further metabolized to benzoic acid. In conclusion, ACNs are bioavailable in rats, and the extent of their metabolism and excretion is based on diet duration. Additionally, urinary hippuric acid content could represent a potential biomarker of ACNs absorption and metabolism in the SD rat under the present experimental conditions.
Being the metabolic syndrome a multifactorial condition, it is difficult to find adequate experimental models to study this pathology. The obese Zucker rats, which are homozygous for the fa allele, present abnormalities similar to those seen in human metabolic syndrome and are a widely extended model of insulin resistance. The usefulness of these rats as a model of non-insulin-dependent diabetes mellitus is nevertheless questionable, and they neither can be considered a clear experimental model of hypertension. Some experimental models different from the obese Zucker rats have also been used to study the metabolic syndrome. Some derive from the spontaneously hypertensive rats (SHR). In this context, the most important are the obese SHR, usually named Koletsky rats. Hyperinsulinism, associated with either normal or slightly elevated levels of blood glucose, is present in these animals, but SHR/N-corpulent rats are a more appropriated model of non-insulin-dependent diabetes mellitus. The SHR/NDmc corpulent rats, a subline of SHR/N-corpulent rats, also exhibit metabolic and histopathologic characteristics associated with human metabolic disorders. A new animal model of the metabolic syndrome, stroke-prone-SHR (SHRSP) fatty rats, was obtained by introducing a segment of the mutant leptin receptor gene from the Zucker line heterozygous for the fa gene mutation into the genetic background of the SHRSP. Very recently, it has been developed as a non-obese rat model with hypertension, fatty liver and characteristics of the metabolic syndrome by transgenic overexpression of a sterol-regulatory element-binding protein in the SHR rats. The Wistar Ottawa Karlsburg W rats are also a new strain that develops a nearly complete metabolic syndrome. Moreover, a new experimental model of low-capacity runner rats has also been developed with elevated blood pressure levels together with the other hallmarks of the metabolic syndrome.
Cardiovascular disease is the leading cause of morbidity and mortality world-wide. The burden of disease is also increasing as a result of the global epidemics of diabetes and obesity. Peroxisome proliferator-activated receptor alpha (PPARalpha), a member of this nuclear receptor family, has emerged as an important player in this scenario, with evidence supporting a central co-ordinated role in the regulation of fatty acid oxidation, lipid and lipoprotein metabolism and inflammatory and vascular responses, all of which would be predicted to reduce atherosclerotic risk. Additionally, the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study has indicated the possibility of preventive effects in diabetes-related microvascular complications, although the mechanisms of these effects warrant further study. The multimodal pharmacological profile of PPARalpha has prompted development of selective PPAR modulators (SPPARMs) to maximise therapeutic potential. It is anticipated that PPARalpha will continue to have important clinical application in addressing the major challenge of cardiometabolic risk associated with type 2 diabetes, obesity and metabolic syndrome.
Lipoprotein lipase (LPL) is a multifunctional enzyme produced by many tissues, including adipose tissue, cardiac and skeletal muscle, islets, and macrophages. LPL is the rate-limiting enzyme for the hydrolysis of the triglyceride (TG) core of circulating TG-rich lipoproteins, chylomicrons, and very low-density lipoproteins (VLDL). LPL-catalyzed reaction products, fatty acids, and monoacylglycerol are in part taken up by the tissues locally and processed differentially; e.g., they are stored as neutral lipids in adipose tissue, oxidized, or stored in skeletal and cardiac muscle or as cholesteryl ester and TG in macrophages. LPL is regulated at transcriptional, posttranscriptional, and posttranslational levels in a tissue-specific manner. Nutrient states and hormonal levels all have divergent effects on the regulation of LPL, and a variety of proteins that interact with LPL to regulate its tissue-specific activity have also been identified. To examine this divergent regulation further, transgenic and knockout murine models of tissue-specific LPL expression have been developed. Mice with overexpression of LPL in skeletal muscle accumulate TG in muscle, develop insulin resistance, are protected from excessive weight gain, and increase their metabolic rate in the cold. Mice with LPL deletion in skeletal muscle have reduced TG accumulation and increased insulin action on glucose transport in muscle. Ultimately, this leads to increased lipid partitioning to other tissues, insulin resistance, and obesity. Mice with LPL deletion in the heart develop hypertriglyceridemia and cardiac dysfunction. The fact that the heart depends increasingly on glucose implies that free fatty acids are not a sufficient fuel for optimal cardiac function. Overall, LPL is a fascinating enzyme that contributes in a pronounced way to normal lipoprotein metabolism, tissue-specific substrate delivery and utilization, and the many aspects of obesity and other metabolic disorders that relate to energy balance, insulin action, and body weight regulation.
Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily and form heterodimers with retinoid X receptor. Three PPAR isoforms have been isolated and termed alpha, beta (or delta) and gamma. Although PPARgamma is expressed predominantly in adipose tissue and associated with adipocyte differentiation and glucose homeostasis, PPARgamma is also present in a variety of cell types. Synthetic antidiabetic thiazolidinediones (TZDs) are well known as ligands and activators for PPARgamma. After it was reported that activation of PPARgamma suppressed production of pro-inflammatory cytokines in activated macrophages, medical interest in PPARgamma has grown and there has been a huge research effort. PPARgamma is currently known to be implicated in various human chronic diseases such as diabetes mellitus, atherosclerosis, rheumatoid arthritis, inflammatory bowel disease, and Alzheimer's disease. Many studies suggest that TZDs not only ameliorate insulin sensitivity, but also have pleiotropic effects on many tissues and cell types. Although activation of PPARgamma seems to have beneficial effects on cardiovascular diseases, the mechanisms by which PPARgamma ligands prevent their development are not fully understood. Recent data about the actions and its mechanisms of PPARgamma-dependent pathway in cardiovascular diseases are discussed here.
The two most commonly used methods to analyze data from real-time, quantitative PCR experiments are absolute quantification and relative quantification. Absolute quantification determines the input copy number, usually by relating the PCR signal to a standard curve. Relative quantification relates the PCR signal of the target transcript in a treatment group to that of another sample such as an untreated control. The 2(-Delta Delta C(T)) method is a convenient way to analyze the relative changes in gene expression from real-time quantitative PCR experiments. The purpose of this report is to present the derivation, assumptions, and applications of the 2(-Delta Delta C(T)) method. In addition, we present the derivation and applications of two variations of the 2(-Delta Delta C(T)) method that may be useful in the analysis of real-time, quantitative PCR data.
Lipid homeostasis in vertebrate cells is regulated by a family of membrane-bound transcription factors designated sterol regulatory element–binding proteins (SREBPs). SREBPs directly activate the expression of more than 30 genes dedicated to the synthesis and uptake of cholesterol, fatty acids, triglycerides, and phospholipids, as well as the NADPH cofactor required to synthesize these molecules (1–4). In the liver, three SREBPs regulate the production of lipids for export into the plasma as lipoproteins and into the bile as micelles. The complex, interdigitated roles of these three SREBPs have been dissected through the study of ten different lines of gene-manipulated mice. These studies form the subject of this review.
Anthocyanins, which are used as a food coloring, are widely distributed in human diets, suggesting that we ingest large amounts of anthocyanins from plant-based foods. Mice were fed control, cyanidin 3-glucoside-rich purple corn color (PCC), high fat (HF) or HF + PCC diet for 12 wk. Dietary PCC significantly suppressed the HF diet-induced increase in body weight gain, and white and brown adipose tissue weights. Feeding the HF diet markedly induced hypertrophy of the adipocytes in the epididymal white adipose tissue compared with the control group. In contrast, the induction did not occur in the HF + PCC group. The HF diet induced hyperglycemia, hyperinsulinemia and hyperleptinemia. These perturbations were completely normalized in rats fed HF + PCC. An increase in the tumor necrosis factor (TNF)-alpha mRNA level occurred in the HF group and was normalized by dietary PCC. These results suggest that dietary PCC may ameliorate HF diet-induced insulin resistance in mice. PCC suppressed the mRNA levels of enzymes involved in fatty acid and triacylglycerol synthesis and lowered the sterol regulatory element binding protein-1 mRNA level in white adipose tissue. These down-regulations may contribute to triacylglycerol accumulation in white adipose tissue. Our findings provide a biochemical and nutritional basis for the use of PCC or anthocyanins as a functional food factor that may have benefits for the prevention of obesity and diabetes.
The transcriptional regulation of lipogenesis is a highly coordinated process occurring in concert with transcriptional as well as post-transcriptional regulation of enzymes involved in glycolysis and gluconeogenesis. Fatty acid synthase (FAS) plays a central role in de novo lipogenesis by converting acetyl-CoA and malonyl-CoA into the final end product, palmitate, which can subsequently be esterified into triacylglycerols and then stored in adipose tissue. Ultimately, this helps to prevent buildup of excess glucose in other types of cells and tissues, the effects of which can be readily observed in the pathophysiology of disease states such as Type-11 diabetes and obesity. Thus, elucidating the transcriptional mechanisms of lipogenic enzyme genes is important for understanding the normal regulation of lipogenesis and ultimately the dysregulation that may occur in certain metabolic disease. In this review, we discuss advances in our understanding of the regulation of lipogenesis at the genetic level, with a special emphasis on the common cis- and trans-acting factors involved in regulation of FAS. Two transcription factors, Upstream Stimulatory Factor (USF) and Sterol Regulatory Element Binding Protein-lc (SREBP-lc), seem to play a dominant and possibly cooperative role in regulating FAS transcription.
Weanling male Sprague-Dawley rats were randomly fed a control diet (AIN-93) (C) or a blueberry diet (B) for 13 weeks, or a reverse diet (R) (C diet for 13 weeks, switched to the B diet for 8 weeks). Aortas were excised, and two intact and two endothelium-denuded rings were immersed in tissue baths containing physiological salt solution at 37 degrees C and aerated with 95% O(2) and 5% CO(2) (pH 7.4). Following equilibration and preconditioning under 1.5-g preload, cumulative dose-response curves were generated with six doses of the alpha1-adrenergic receptor-selective agonist L-phenylephrine (L-Phe, 10(8)-3 x 10(-6) M) and relaxed with one dose of acetylcholine (3 x 10(-6) M) to assess intact endothelium. The maximum force of contraction (Fmax) and vessel sensitivity (pD(2)) were determined in intact and endothelium-denuded rings. A two-way analysis of variance test revealed that blueberry-fed animals (B and R diets) developed a significantly lower F (max) (0.873 +/- 0.0463 and 0.9266 +/- 0.0463 g, respectively) when contracted with L-Phe, compared with the animals on the C diet (1.109 +/- 0.0463 g) (P < .05). The pD(2) of the intact rings was not significantly different among diet groups. Additionally, diet did not significantly affect the mean F (max) or pD(2) of endothelium-denuded rings. Our results indicate for the first time that wild blueberries incorporated into the diet affect the vascular smooth muscle contractile machinery by suppressing the alpha1-adrenergic receptor agonist-mediated contraction while having no effect on membrane sensitivity of the endothelial or vascular smooth muscle cell layer. Furthermore, their mechanism of action seems to be accomplished through an endothelium-dependent pathway.
Adipocyte dysfunction is strongly associated with the development of obesity and insulin resistance. It is accepted that the regulation of adipocytokine secretion or the adipocyte specific gene expression is one of the most important targets for the prevention of obesity and amelioration of insulin sensitivity. Recently, we demonstrated that anthocyanins, which are pigments widespread in the plant kingdom, have the potency of anti-obesity in mice and the enhancement adipocytokine secretion and adipocyte gene expression in adipocytes. In this study, we have shown for the first time the gene expression profile in isolated rat adipocytes treated with anthocyanins (cyanidin 3-glucoside; C3G or cyanidin; Cy). The rat adipocytes were treated with 100 muM C3G, Cy or vehicle for 24 h. The total RNA from the adipocytes was isolated and carried out GeneChip microarray analysis. A total of 633 or 427 genes was up-regulated (>1.5-fold) by the treatment of adipocytes with C3G or Cy, respectively. The up-regulated genes include lipid metabolism and signal transduction-related genes, however, the altered genes were partly different between the C3G- and Cy-treated groups. Based on the gene expression profile, we demonstrated the up-regulation of hormone sensitive lipase and enhancement of the lipolytic activity by the treatment of adipocytes with C3G or Cy. These data have provided an overview of the gene expression profiles in adipocytes treated with anthocyanins and identified new responsive genes with potentially important functions in adipocytes related with obesity and diabetes that merit further investigation.
Total, Insoluble and Soluble Dietary Fiber in Food – Enzymatic-Gravimetric Method, MES-TRIS Buffer. Official Methods of Analysis
AOAC Method 991.43 (1995) Total, Insoluble and Soluble
Dietary Fiber in Food – Enzymatic-Gravimetric Method,
MES-TRIS Buffer. Official Methods of Analysis, 16th ed.
Gaithersburg, MD: AOAC International.
SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver Peroxisome proliferator-activated receptor alpha (PPAR-a): at the crossroads of obesity, diabetes and cardiovascular disease
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29. Fruchart JC (2009) Peroxisome proliferator-activated
receptor alpha (PPAR-a): at the crossroads of obesity, diabetes and cardiovascular disease. Atherosclerosis 205, 1–8.
Total, Insoluble and Soluble Dietary Fiber in Food -Enzymatic-Gravimetric Method
- Mes-Tris Buffer
AOAC Method 991.43 (1995) Total, Insoluble and Soluble
Dietary Fiber in Food -Enzymatic-Gravimetric Method,
MES-TRIS Buffer. Official Methods of Analysis, 16th ed.
Gaithersburg, MD: AOAC International.