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Anti-obesity effect of cocoa proteins (Theobroma cacao L.) variety “Criollo” and the expression of genes related to the dysfunction of white adipose tissue in high-fat diet-induced obese rats
Abstract
The objective of this work was to evaluate if Cocoa Proteins (CP) from the cocoa-bean were able to reduce factors related to obesity and activated related gene targets against white adipose tissue (WAT) dysfunction in a rat model of hypercaloric diet-induced obesity. The results showed that the administration with 150 mg/kg/day of CP on a hypercaloric diet reduces body-weight gain, relative weight of WAT, serum triglycerides, NEFAs, insulin, and leptin levels, and pro-inflammatory factors, with an increase in serum HDL levels, activation (AMPK, PPAR-γ, PPAR-α, SIRT1, Plin1, and PGC-1α) and repression (TNF-α, SREBP-1c, Leptin and ACC) of the mRNA of transcription factors and proteins related to WAT dysfunction. The CP prevented dysfunction in WAT who is related to obesity by down-regulation of factors related to lipogenesis and up-regulation of those related to energy expenditure, lowering the release of triglycerides and NEFAs into peripheral tissues, thus decreasing pro-inflammatory processes.
... Coronado-Cáceres et al. evaluated the properties of cocoa proteins to reduce factors related to obesity and turn on related genes targets against white adipose tissue (WAT) dysfunction in a murine obesity model [29]. Among the results, the supplementation with cocoa proteins prevent body weight gain, reduces serum triglycerides, insulin, leptin, and non-esterified fatty acid levels, and pro-inflammatory molecules; on the other hand, cocoa proteins increase HDL levels, the supplementation upregulated PPARG, PPARα, AMPK, Plin1, SIRT1 and PGC-1α, and downregulated TNF-α, Leptin, ACC, and SREBP-1c, molecules related to WAT dysfunction related to obesity. ...
... Among the results, the supplementation with cocoa proteins prevent body weight gain, reduces serum triglycerides, insulin, leptin, and non-esterified fatty acid levels, and pro-inflammatory molecules; on the other hand, cocoa proteins increase HDL levels, the supplementation upregulated PPARG, PPARα, AMPK, Plin1, SIRT1 and PGC-1α, and downregulated TNF-α, Leptin, ACC, and SREBP-1c, molecules related to WAT dysfunction related to obesity. Cocoa proteins downregulated factors related to lipogenesis and upregulated molecules related to energy expenditure, reducing the systemic release of triglycerides and non-esterified fatty acid, and decreasing the pro-inflammatory response [29]. The same group of researchers from Coronado-Cáceres published in 2021 results of their research focused on the effect of cocoa proteins on blood pressure. ...
... Coronado-Cáceres et al. [29] Rosas et al. [23] Oral supplementation of 4% nopal in obese Zucker rats. ...
Adipose tissue and liver metabolism play a key role in maintaining body homeostasis;therefore, their impairment conduces a pathological state. Nowadays, occidental lifestyle is a commonetiological issue among a variety of chronic diseases, while diet is a unique strategy to prevent obesityand liver metabolism impairment and is a powerful player in the treatment of metabolic-relateddiseases. Mesoamerican foods are rich in bioactive molecules that enhance and improve adiposetissue and liver performance and represent a prophylactic and therapeutic alternative for disordersrelated to the loss of homeostasis in the metabolism of these two important tissues.
(3) (PDF) Citation: medicina Effects of Foods of Mesoamerican Origin in Adipose Tissue and Liver-Related Metabolism. Available from: https://www.researchgate.net/publication/375635711_Citation_medicina_Effects_of_Foods_of_Mesoamerican_Origin_in_Adipose_Tissue_and_Liver-Related_Metabolism [accessed Nov 23 2023].
... Coronado-Cáceres et al. evaluated the properties of cocoa proteins to reduce factors related to obesity and turn on related genes targets against white adipose tissue (WAT) dysfunction in a murine obesity model [29]. Among the results, the supplementation with cocoa proteins prevent body weight gain, reduces serum triglycerides, insulin, leptin, and non-esterified fatty acid levels, and pro-inflammatory molecules; on the other hand, cocoa proteins increase HDL levels, the supplementation upregulated PPARG, PPARα, AMPK, Plin1, SIRT1 and PGC-1α, and downregulated TNF-α, Leptin, ACC, and SREBP-1c, molecules related to WAT dysfunction related to obesity. ...
... Among the results, the supplementation with cocoa proteins prevent body weight gain, reduces serum triglycerides, insulin, leptin, and non-esterified fatty acid levels, and pro-inflammatory molecules; on the other hand, cocoa proteins increase HDL levels, the supplementation upregulated PPARG, PPARα, AMPK, Plin1, SIRT1 and PGC-1α, and downregulated TNF-α, Leptin, ACC, and SREBP-1c, molecules related to WAT dysfunction related to obesity. Cocoa proteins downregulated factors related to lipogenesis and upregulated molecules related to energy expenditure, reducing the systemic release of triglycerides and non-esterified fatty acid, and decreasing the pro-inflammatory response [29]. The same group of researchers from Coronado-Cáceres published in 2021 results of their research focused on the effect of cocoa proteins on blood pressure. ...
... Coronado-Cáceres et al. [29] Rosas et al. [23] Oral supplementation of 4% nopal in obese Zucker rats. ...
Adipose tissue and liver metabolism play a key role in maintaining body homeostasis; therefore, their impairment conduces a pathological state. Nowadays, occidental lifestyle is a common etiological issue among a variety of chronic diseases, while diet is a unique strategy to prevent obesity and liver metabolism impairment and is a powerful player in the treatment of metabolic-related diseases. Mesoamerican foods are rich in bioactive molecules that enhance and improve adipose tissue and liver performance and represent a prophylactic and therapeutic alternative for disorders related to the loss of homeostasis in the metabolism of these two important tissues.
... Long-term polyphenol consumption has been associated with several health benefits (Cory et al., 2018). For example, diets rich in flavanols, a subgroup of flavonoids found in green tea, some vegetables, and abundantly present in cocoa, have proven to be an important strategy for reducing the risk of developing obesity (Coronado-Cáceres et al., 2019), diabetes mellitus (Ramos et al., 2017), and cardiovascular diseases (Ludovici et al., 2017). ...
... Attenuated body weight gain and the reduced adiposity index following COCOA and/or EXE have been attributed to several physiological mechanisms, depending on dosage and the total duration of intervention. These include the suppression of factors related to lipogenesis, such as SREBP-1c and acetyl Co-A carboxylase (Coronado-Cáceres et al., 2019) and the activation of the factors involved in energy expenditure, including peroxisome proliferator-activated receptor-gamma, sirtuin 1, uncoupling protein 1, and peroxisome proliferator-activated receptor-gamma coactivator-1α (Rabadan-Chávez et al., 2016). In addition, the beneficial effects of COCOA and/or EXE may be mediated via appetite suppression through different hormones, such as increased Glucagon-like peptide-1 (GLP-1) (Strat et al., 2016) and decreased ghrelin concentrations (Massolt et al., 2010), as well as enhanced leptin and reduced adiponectin levels (Flores, 2019). ...
... The reduction in circulating leptin concentrations mediated by COCOA and EXE is associated with changes in body composition, specifically lowering the percentage of body fat and reducing the adipocyte size (Coronado-Cáceres et al., 2019;Fedewa et al., 2018). Moreover, leptin has known pleiotropic effects, such as neuroendocrine regulation, glucose homeostasis, as well as modulation of the reproductive and hematopoietic system, inflammation, and immune system (Abella et al., 2017). ...
We aimed to investigate the combined effects of aerobic exercise (EXE) and cocoa flavanol (COCOA) supplementation on performance, metabolic parameters, and inflammatory and lipid profiles in obese insulin-resistant rats. Therefore, 32 male Wistar rats (230–250 g) were fed a high-fat diet and a fructose-rich beverage for 30 days to induce insulin resistance. Next, the rats were randomized into four groups, orally administered placebo solution or COCOA supplementation (45 mg·kg ⁻¹ ), and either remained sedentary or were subjected to EXE on a treadmill at 60% peak velocity for 30 min, for 8 weeks. Blood samples and peripheral tissues were collected and processed to analyze metabolic and inflammatory parameters, lipid profiles, and morphological parameters. Supplementation with COCOA and EXE improved physical performance and attenuated body mass gain, adipose index, and adipocyte area. When analyzed as individual interventions, supplementation with COCOA and EXE improved glucose intolerance and the lipid profile reduced the concentrations of leptin, glucose, and insulin, and reduced homeostasis assessment index (all effects were p < .001 for both interventions), while ameliorated some inflammatory mediators in examined tissues. In skeletal muscles, both COCOA supplementation and EXE increased the expression of glucose transporter ( p < .001 and p < .001), and combined intervention showed additive effects ( p < .001 vs. COCOA alone or EXE alone). Thus, combining COCOA with EXE represents an effective nonpharmacological strategy to treat insulin resistance; it could prevent Type 2 diabetes mellitus by improving physical performance, glucose metabolism, neuroendocrine control, and lipid and inflammatory mediators in the liver, pancreas, adipose tissue, and skeletal muscle in obese male insulin-resistant rats.
... The coat and the mucilage of pods-derived seeds were removed, seeds were lyophilized and ground, and the flour was defatted in three phases: flour was dissolved in hexane:chloroform (2:1, v/v) at ratio 1:15 (w/v), magnetically stirred for 90 min, and centrifuged at 4700× g for 20 min at 4 • C [20]. The pellet was collected and dried in the extraction hood. ...
... The rats were acclimatized for one week with unlimited access to food and water. A total of 21 rats were used and randomly divided into three dietary groups (n = 7 per group) as follows [20,35]: Standard Diet (STD group, 3.1 kcal/g) (TD.05230; Teklad Global Harlan Laboratories, Inc., Madison, WI, USA), High-Fat diet (HF group, 4.5 kcal/g) (TD.88137; ...
... All animals were fed ad libitum with free access to water during the experimental period (8 weeks). The use of male Wistar rats was approved by the Ethics and Research Committee of the National School of Biological Sciences of the National Polytechnic Institute from Mexico [18,20,35,36]. ...
This study aimed at determining the effect of cocoa proteins (CP) on the blood pressure, using in silico, in vitro and in vivo approaches. The in silico assay showed 26 Criollo cocoa peptides with alignment in the Blast® analysis. Peptide sequences ranged from 6 to 16 amino acids, with molecular weight ranging from 560.31 to 1548.76 Da. The peptide sequences LSPGGAAV, TSVSGAGGPGAGR, and TLGNPAAAGPF showed the highest theoretical affinity with −8.6, −5.0, and −10.2 kcal/mol, for the angiotensin-converting enzyme (ACE), renin, and angiotensin II type 1 receptor (AT1-R), respectively. The Criollo CP hydrolysates (CPH) presented in vitro ACE inhibitory activity with an IC50 value of 0.49 mg/mL. Furthermore, the orogastric administration of 150 mg CP/kg/day in rats fed a high-fat (HF) diet (HF + CP group) showed a significant decrease in systolic blood pressure (SBP) by 5% (p < 0.001) and diastolic blood pressure (DBP) by 7% (p < 0.001) compared with the HF group. The human equivalent dose (HED) of CP for an adult (60 kg) is 1.45 g per day. These results suggest that the consumption of CP could reduce blood pressure by blocking ACE, and could be used as an ingredient in the elaboration of antihypertensive functional foods.
... The PPARγ ligand plays a key role because of its ability of lower plasma triglyceride levels and increase HDLcholesterol [86]. Cocoa enhanced the expression of PPARγ levels related to the high-fat group, in association with a diminution of serum triglycerides and FFA levels [87]. The latter are PGC1α, which can bind to and co-activate PPARγ to contribute to the transports and use of fatty acids [88]. ...
... Another strategy is based on the AMP-activated protein kinase (AMPK) pathway. After consuming cocoa in high-fat diet, the expression of AMPK was superior to that of the standard group, suggesting that the AMPK pathway could be activated by cocoa [87]. This enzyme is related to the promotion of β-oxidation, lipogenesis of FFA and lipogenic and fatty oxidation enzymes activities. ...
... Upregulation of the gene expression of IgE receptor FcεRI, decrease of rat mast cell protease II (RMCP-II) levels, prevention of the synthesis and decrease of anti-ovalbumin IgE, [80] Obesity Reduction of adiposity, dyslipidemia, plasma triglyceride levels and increase HDL-cholesterol Upregulation of PPARγ, PGC1α and SIRT1 [86][87][88] Reduction in lipid accumulation and inhibition of the differentiation of preadipocytes Decrease the expression of PPARγ and C/EBPα and C/EBPβ, activation of AMPK and inhibition of the JNK pathway [89,90] Promotion of β-oxidation, lipogenesis of FFA and activation of lipogenic and fatty oxidation enzymes Activation of AMPK pathway, Down-regulation of the expression of Acaca Mcat, Fasn and Scd1 genes [87,91] Improve lipolysis pathway and release of FFA and glycerol Antagonism potential of adenosine receptors, Enhance the effects of catecholamines, Modulation of the release of noradrenalin, Activation of β-adrenergic receptors [93] Influence satiety and energy expenditure, reduce hypercaloric diet induced-leptin resistance, activation of fat body loss Down regulation of leptin gene expression [94] Diabetes Prevention against ECM accumulation of kidney Increase of SIRT-1 level by reducing activation of NOX-4 which have blocked the PARP-1 activation and restoration of NAD + levels [97] Protection against death-inducing factors on β-cells, Reduction of apoptosis of β-cell mass and delay on the progression of T2D ...
Theobroma cacao L. is an ancestral cultivated plant which has been consumed by various populations throughout history. Cocoa beans are the basic material occurring in the most consumed product in the world, namely chocolate. Their composition includes polyphenols, methylxanthines, lipids and other compounds that may vary qualitatively and quantitatively according to criteria such as variety or culture area. Polyphenols and methylxanthines are known as being responsible for many health benefits, particularly by preventing cardiovascular and neurodegenerative diseases. Recent studies emphasized their positive role in dietary metabolic disorders, such as diabetes and weight gain. After a brief presentation of cocoa bean, this review provides an overview of recent research activities highlighting promising strategies which modulated and prevented gastro-intestinal metabolism dysfunctions.
... Cocoa proteins (CP) and their hydrolysates have been reported to exert antioxidant and antitumor effects [16,17]. Also, the nutrigenomic effects of CP against white adipose tissue (WAT) dysfunction with reduction in inflammatory factors, triglyceride levels, and non-esterified fatty acids (NEFAs) in serum, as well as decrease in body weight and different WATs have been shown [18]. Also, other investigations have suggested the contribution of CP to the release of flavor precursor peptides [10,19]. ...
... Feed consumption was monitored daily, and body weight was measured weekly throughout the experiment. After the experimental period (week 8), rats were anesthetized with pentobarbital sodium (32 mg/kg intraperitoneally) after 12 h fasting [18,[26][27][28]. The use of male Wistar rats was approved by the Ethics and Research Committee of the National School of Biological Sciences of National Polytechnic Institute from Mexico. ...
... A recent study performed in rats fed a hypercaloric diet has shown that CP decrease body weight gain [18] in spite of consuming the same amount of food, indicating that the decrease in body weight was not due to appetite suppression. The results suggest a potential mechanism involving PL inhibition. ...
The aim of this study was to determine the pancreatic lipase (PL) inhibitory effect of cocoa protein (CP) hydrolysates (CPH) using in silico and in vitro approaches, and an in vivo high-fat diet (HF) obese rat model. The results showed better theoretical affinity on PL for cocoa peptides EEQR, GGER, QTGVQ, and VSTDVNIE released from vicilin and albumins (−6.5, −6.3, −6.2, and −6.1 kcal/mol, respectively). Absorption, distribution, metabolism, and excretion (ADMET) prediction showed the human intestinal absorption (HIA) capacity of orlistat and eight cocoa peptides, demonstrating that they presented a low probability of toxicity with values lower than 0.6, while the orlistat has a high probability of hepatotoxicity with a mean value of 0.9. CPH (degree of hydrolysis of 55%) inhibited PL with an IC50 (concentration needed to inhibit 50% of enzyme activity) value of 1.38 mg/mL. The intragastric administration of 150 mg CP/kg/day to rats increased total lipids and triglycerides excretion in feces, ranging from 11% to 15% compared to the HF-diet. The HF + CP-diet also significantly decreased (p < 0.05) the apparent rate of fat absorption compared with the HF group. These results suggest that CP has anti-obesity potential by inhibiting PL, thus helping to prevent the development of non-communicable diseases.
... La extracción de las proteínas se realizó siguiendo el método de [13] con algunas modificaciones. A partir del acdp, las fracciones de albúmina (Alb) y globulina (Glob), se extrajeron sucesivamente con Tris-hcl 10 mM, pH 7.5 (que contiene edta 2 mM) y cloruro de sodio 0.5 M (que contiene edta 2 mM y Tris-hcl 10 La mezcla se agitó en vortex (hasta que se mostró transparente) y se centrifugó a 1000 rpm por 5 minutos. Finalmente, en el sobrenadante se realizó la medición de la absorbancia a 382 nm, previa elaboración de una curva patrón de ácido hipúrico (0 -50 µg). ...
... Asimismo, el segundo componente por abundancia es la proteína (10-15 %), la cual se constituye por cuatro fracciones: albúmina, globulina, prolamina y glutelina [8].Actualmente, la variedad forastero representa aproximadamente el 70 % de la producción mundial del cacao y se cultiva en los estados de Chiapas y Tabasco [9]; se caracteriza por su resistencia a enfermedades, baja demanda de nutrientes y alto rendimiento de frutos, a diferencia de la variedad criollo.Los efectos bio-funcionales del cacao están relacionados con los compuestos fenólicos, aunque en años recientes las proteínas y los péptidos derivados de las mismas han cobrado importancia. Debido a sus propiedades antioxidantes [8], antitumorales [9], antiadipogénicas[10] y antihipertensivas[11], son aprovechables en la prevención de enfermedades crónico-degenerativas como la diabetes, cáncer, obesidad e hipertensión.Hasta la fecha, la actividad antihipertensiva del cacao se ha determinado específicamente en la variedad criollo (que debido a sus características organolépticas se destina principalmente a la elaboración de chocolates de alta calidad)[11]. Por lo anterior, este trabajo pretende evaluar in vitro la albúmina y globulina obtenidas del cacao forastero, sus hidrolizados enzimáticos y fracciones de péptidos en términos de la capacidad para inhibir la eca. ...
According to reports from the World Health Organization (WHO), hypertension is considered the most common cardiovascular risk factor, affecting 25 to 30% of the world's population. One of the primary causes of hypertension is angiotensin-converting enzyme-I (ACE), which plays a crucial role in regulating blood pressure through the modulation of the renin-angiotensin-aldosterone system. Consequently, there is a wide range of drugs available that can inhibit ACE. However, these drugs can cause adverse side effects such as cough, headache, skin rash, altered taste, angioedema, nausea, and allergic reactions. For this reason, there is considerable interest in obtaining ACE inhibitors from natural sources that reduce side effects and dependence on drugs. Specifically, bioactive peptides present in enzymatic protein hydrolysates have shown anti-hypertensive properties by inhibiting ACE, making them a promising alternative in the prevention and treatment of hypertension. The objective of this study was to evaluate the ACE inhibitory activity (in vitro) of enzymatic hydrolysates obtained from cocoa bean proteins (albumin and globulin), with the purpose of considering them as a natural source of potential anti-hypertensive agents. The results demonstrated that the enzymatic treatment (with alcalase) of albumin and globulin from cocoa beans is a viable bioprocess for producing hydrolysates with ACE inhibitory activity. In particular, hydrolysates and peptide fractions (< 3000 Da) with greater ACE inhibitory capacity were generated from globulin, making them a suitable choice for designing functional foods.
... In studies conducted with the daily intake of 2 g up to 100 g of cocoa or dark chocolate (with 50-90 % and 13 % flavonoids) for 15 days up to 6 months, a decrease in adipose tissue was quantified, in healthy, overweight or obese population, determined by the indicators of body weight, BMI, CC and the ratio of waist hip index (Nour-Rahman et al., 2019) and it has been reported that this effect is attributed to the content of polyphenols present in cocoa, so its daily intake, improves the expression of peroxisome proliferator-activated receptor (PPARγ) levels, decreasing serum levels of triglycerides and free fatty acids, the latter are coactivators of 1 α peroxisome proliferator-activated receptor-activated receptor (PGC1α), which can bind and coactivate PPARγ, and increase transport and metabolize to fatty acids (Leyva-Soto et al., 2018;Rahman et al., 2018). In addition, PGC1α interact with sirtuin 1 (SIRT1), regulating energy homeostasis, which increase energy expenditure, and energy storage in white adipose tissue, thus decreasing adipose tissue and dyslipidemia (Leyva-Soto et al., 2018;Rahman et al., 2018;Coronado-Cáceres et al., 2019). ...
... On the other hand, according to the American Council on Exercise (2009) the students who participated in this work, are within the classification, fitness body fat percentage (14-17 %) and average (25-31 %) respectively. From the above, cocoa and its polyphenol content, although they can modulate the expression of PGC1α, SIRT1 and PPARγ in white adipose tissue [8], it is suggested that students, increase the energy expenditure of their metabolism, to balance the percentage and kilograms of body fat, and decrease the risk of obesity, which will influence alterations in lipid profile, arterial hypertension and diabetes mellitus in the future (Leyva-Soto et al., 2018;Rahman et al., 2018;Coronado-Cáceres et al., 2019). ...
University students are vulnerable to developing metabolic syndrome, due to the low consumption of foods with bioactive properties. Cocoa paste containing phenols (CPCP) may prevent it. The objective of the study was to evaluate the effect of consuming 1 g of cocoa paste for 4 weeks on anthropometric indicators, body composition, blood pressure and heart rate in university students. The population consisted of 7 men and 13 women. In the post-test measurement, students had the best result in weight (74.4-72.3 kg), BMI (26.0-25.2 kg/m 2) and WC (85.5-83.5 cm), and in the body composition, only in the percentage of fat mass (62.3-60.9 %) there were significant differences (p>0.05). CPCP consumption in females decreased systolic and diastolic blood pressure (107.0 vs 100.0, p=0.023) and (76.0 vs 71.0, p=0.007) respectively. CPCP has a protective effect and may exert a preventive function.
... The anti-obesogenic effect of cocoa proteins (CP) has also been reported (Coronado-Cáceres et al., 2019). After the administration during 8-weeks of 150 mg/kg/day of CP to diet-induced obesity of male Wistar rats fed with a high fat diet (HF), results showed that total weight gain and relative weight on white adipose tissue (WAT) were significantly lower than rats administered with HF diet. ...
... Contrary to this, TNF-α, SREBP-1c, leptin and ACC of the mRNA of transcription factors and proteins related to WAT dysfunction were repressed. Overall, these results suggested that the administration of cocoa proteins may help decrease the development of inflammatory diseases related to obesity (Coronado-Cáceres et al., 2019). Although authors attributed the antiobesogenic effect and the potential mechanistic pathway on the administration of cocoa proteins, it should not be overlooked that bioactive peptides are released through gastrointestinal digestion and these may be having the effect. ...
Post-harvest processing of cocoa beans, such as fermentation, not only determines the formation of aroma and flavor compounds, but also contributes to the formation of bioactive compounds with health benefits. Nevertheless, most studies associate these beneficial effects to the polyphenols present and little is known about the potential health effects of other cocoa components such as bioactive peptides. Thus, in the present review we focus on the role of cocoa bean protein hydrolysis for the release of bioactive peptides. Also, the potential health benefits of cocoa bean hydrolysates and peptides, specifically, antioxidant, antihypertensive, antidiabetic, anti-Alzheimer, antiobesogenic and antitumor activities are presented. However, more research is needed that considers bioaccesibility and bioavailability studies, as well as in vivo studies and clinical trials, for testing cocoa bean bioactive peptides. This knowledge may allow the development of nutraceuticals and food products with specific biological activities as well as good aroma and flavor.
... Several studies have identified peptide sequences in cocoa bean proteins that may offer various health benefits when released. [104][105][106][107][108] These studies have focused on bioactive peptides released through three methods: 1) cocoa bean autolysis, 105 2) hydrolysis with exogenous commercial enzymes, 106,107 and 3) fermentation of cocoa beans. 98,100,104 Numerous antioxidant peptides from various food proteins have been identified, and their antioxidant properties have been examined. ...
Numerous studies have identified cocoa phenolics, procyanidins, and flavan-3-ols as bioactive antioxidant compounds that enhance vascular function, reduce inflammation, and improve lipid metabolism, insulin sensitivity, and platelet aggregation. Research indicates that consuming flavanol-rich cocoa supports cardiovascular health. Given the rising global occurrence of cardiovascular disease and its related risk factors, this review article aimed to investigate the impact of chocolate/cocoa intake on cardio and cerebrovascular conditions and their related risks. Across various clinical trials, moderate flavonol-rich cocoa/chocolate consumption proved to be correlated with better heart health. Advantages include a diminished risk of heart failure, hypertension, platelet aggregation, coronary artery disease, stroke, atrial fibrillation, high cholesterol, and peripheral artery disease. Consuming 50 grams of dark chocolate daily or every other day has been linked to these positive outcomes. While flavanol-rich chocolate shows potential as a complementary therapy for various cardio and cerebrovascular conditions, extensive clinical trials are necessary to confirm its effectiveness.
... Moreover, the flavonoid-enriched diet from conventional cocoa has also been evidenced to downregulate the expression of genes involved in lipid metabolism in colonic samples [5] and to reduce fat deposition [6]. Likewise, anti-obesity activity has also been attributed to cocoa due to their impact on the expression of genes related to lipid metabolism in white adipose tissue [7]. Therefore, further research should be performed in order to identify the compounds responsible for these effects and to elucidate the mechanisms involved. ...
... Both TNF-α protein and mRNA levels thereof measured in white adipose tissue and the pro-inflammatory chemokine MCP-1 decreased when cocoa protein was administered in rats after a high fat diet [83]. Besides that, the secretion and the mRNA levels of pro-inflammatory cytokines as TNF-α and IL-6 were inhibited by theobromine treatment [28]. ...
Dietary phenolic compounds are considered as bioactive compounds that have effects in different chronic disorders related to oxidative stress, inflammation process, or aging. These compounds, coming from a wide range of natural sources, have shown a pleiotropic behavior on key proteins that act as regulators. In this sense, this review aims to compile information on the effect exerted by the phenolic compounds and their metabolites on the main metabolic pathways involved in energy metabolism, inflammatory response, aging and their relationship with the biological properties reported in high prevalence chronic diseases. Numerous in vitro and in vivo studies have demonstrated their pleiotropic molecular mechanisms of action and these findings raise the possibility that phenolic compounds have a wide variety of roles in different targets.
En la producción mundial del cacao se han identificado tres tipos u orígenes genéticos (Forastero, Criollo y Trinitario). El cacao Criollo se ha clasificado como cacao fino de aroma debido a su perfil aromático y sensorial. Los granos presentan menor astringencia y amargor comparado con el cacao Forastero, por lo que su uso se ha delimitado a la chocolatería fina, alcanzan-do un mayor valor en el mercado. El cacao Criollo se produce principalmente en Centro América y Sudamérica. En México, el cacao Criollo es cultivado en los estados de Tabasco y Chiapas principalmente. Hoy en día este cacao ha tomado especial relevancia debido a que, además de presentar un perfil sensorial con notas florales, dulces, frutales y menos amargas, ha demostrado que puede llegar a ser una buena fuente de compuestos fenólicos y péptidos bioactivos que pueden proveer beneficios a la salud.
Nesta obra, exploramos as diversas dimensões que compõem o equilíbrio físico e emocional. Em um contexto em constante evolução, cada capítulo revela a importância de uma visão holística na promoção do bem-estar. Ao longo das páginas, encontramos reflexões sobre práticas inovadoras, como o uso de oficinas e arteterapia no atendimento a mulheres em situação de violência. Essas abordagens terapêuticas se destacam como ferramentas valiosas na reconstrução emocional. A complexidade da farmacoterapia em pacientes pediátricos transplantados hepáticos é abordada, evidenciando os desafios e avanços na adaptação de doses para essa população sensível. Este olhar aprofundado revela a necessidade de personalização no tratamento. A farmácia clínica, por sua vez, desempenha um papel crucial no ajuste de medicamentos em terapia renal substitutiva. A sensibilidade desse contexto demanda cuidados específicos, ressaltando a importância de uma abordagem personalizada e eficaz. [...]
Nesta obra, exploramos as diversas dimensões que compõem o equilíbrio físico e emocional. Em um contexto em constante evolução, cada capítulo revela a importância de uma visão holística na promoção do bem-estar. Ao longo das páginas, encontramos reflexões sobre práticas inovadoras, como o uso de oficinas e arteterapia no atendimento a mulheres em situação de violência. Essas abordagens terapêuticas se destacam como ferramentas valiosas na reconstrução emocional. A complexidade da farmacoterapia em pacientes pediátricos transplantados hepáticos é abordada, evidenciando os desafios e avanços na adaptação de doses para essa população sensível. Este olhar aprofundado revela a necessidade de personalização no tratamento. A farmácia clínica, por sua vez, desempenha um papel crucial no ajuste de medicamentos em terapia renal substitutiva. A sensibilidade desse contexto demanda cuidados específicos, ressaltando a importância de uma abordagem personalizada e eficaz. [...]
This volume is a complete review of the cutting-edge scientific evidence about the isolation, identification, bioactivity and molecular analysis of the biologically active peptides (BAPs) obtained from several underutilized grains.
It provides a general review of current and new technologies in isolating and bioprospecting BAPs before going into the details of 11 grains. Amaranth, quinoa, millet, buckwheat, sorghum, lupin, mung bean, chickpea, broad bean, cocoa bean and chia are extensively discussed in dedicated chapters. Additionally, these chapters provide information about the characteristics of the crop, its main varieties, traditional uses, economic importance, nutritional aspects, structure and chemical composition of the grains, as well as the classification and distribution of the grain protein fractions. Moreover, the advances in the analytical techniques used for the concentration, purification and molecular characterization of BAPs are described. The impact of BAPs in the promotion of health is highlighted, as well as their potential incorporation as promising ingredients in the development of functional foods, nutraceuticals and cosmeceuticals. Finally, the main findings related to the potential antiviral and anti-COVID-19 activities of BAPs derived from underutilized grains are described.
This reference will be of interest for academics, professionals and researchers focused in food science, biotechnology, pharmacology and agriculture, and to professionals involved in the research and development of natural products, pharmaceuticals and cosmeceuticals.
Background
Obesity is a complex health and global epidemic issue. It is an increasing global health challenge covering significant social and economic costs. Abnormal accumulation of fat in the body may increase the health risks including diabetes, hypertension, osteoarthritis, sleep apnea, cardiovascular diseases, stroke and cancer. Synthetic drugs available on the market reported to have several side effects. Therefore, the management of obesity got to involve the traditional use of medicinal plants which helps to search the new therapeutic targets and supports the research and development of anti-obesity drugs.
Objective
This review aim to update the data and provide a comprehensive report of currently available knowledge of medicinal plants and phyto-chemical constituents reported for their anti-obesity activity.
Methodology
An electronic search of the periodical databases like Web of Science, Scopus, PubMed, Scielo, Niscair, ScienceDirect, Springerlink, Wiley, SciFinder and Google Scholar with information reported the period 1991-2019, was used to retrieve published data.
Results
A comprehensive report of the present review manuscript is an attempt to list the medicinal plants with anti-obesity activity. The review focused on plant extracts, isolated chemical compounds with their mechanism of action and their preclinical experimental model, clinical studies for further scientific research.
Conclusion
This review is the compilation of the medicinal plants and their constituents reported for the managements of obesity. The data will fascinate the researcher to initiate further research that may lead to the drug for the management of obesity and their associated secondary complications. Several herbal plants and their respective lead constituents were also screened by preclinical In-vitro and In-vivo, clinical trials and are effective in the treatment of obesity. Therefore, there is a need to develop and screen large number of plant extracts and this approach can surely be a driving force for the discovery of anti-obesity drugs from medicinal plants.
Sixteen kinds of non-volatile fat-soluble substances were isolated from the Haihong fruit wine by organic solvent extraction and chromatographic techniques. The structures of 13 compounds were identified by means of mass spectrometry and nuclear magnetic resonance. The relationship between the pharmacological effects of Haihong fruit wine and its active substances such as hyperoside, rutin, catechin, epicatechin, and β-sitosterol was investigated. Results showed that the contents of hyperin, rutin, catechin, epicatechin, naringin dihydrochalcone, β-sterol and other polyphenol flavonoids in the Haihong fruit wine could significantly improve the lipid metabolism of hyperlipidemic mice, increase high-density lipoprotein, reduce blood viscosity, and significantly prevent platelet aggregation and fat accumulation in the liver of mice. The strong reduction and chelation of phenolic hydroxyl groups in hyperin, catechin and rutin are the essential reasons for the pharmacological effects of the fruit wine. These substances can exert their pharmacological effects by eliminating excess free radicals of ·DPPH, ·OH, and ·O2⁻ and by complexing metal ion catalysts which are conducive to the formation of free radicals.
The protein fractions of cocoa have been implicated influencing both the bioactive potential and sensory properties of cocoa and cocoa products. The objective of the present review is to show the impact of different stages of cultivation and processing with regard to the changes induced in the protein fractions. Special focus has been laid on the major seed storage proteins throughout the different stages of processing. The study starts with classical introduction of the extraction and the characterization methods used, while addressing classification approaches of cocoa proteins evolved during the timeline. The changes in protein composition during ripening and maturation of cocoa seeds, together with the possible modifications during the post-harvest processing (fermentation, drying, and roasting), have been documented. Finally, the bioactive potential arising directly or indirectly from cocoa proteins has been elucidated. The “state of the art” suggests that exploration of other potentially bioactive components in cocoa needs to be undertaken, while considering the complexity of reaction products occurring during the roasting phase of the post-harvest processing. Finally, the utilization of partially processed cocoa beans (e.g., fermented, conciliatory thermal treatment) can be recommended, providing a large reservoir of bioactive potentials arising from the protein components that could be instrumented in functionalizing foods.
Enzymatic thornback ray (Raja clavata) muscle hydrolysates have been shown to have antioxidant and antihypertensive activities in vitro. The Neutrase hydrolysate exhibited the highest activities, so it was investigated along with the undigested muscle to test their hypolipidemic, antioxidative and fertility effects in rats fed with a high-cholesterol diet (HCD). Animals were allocated into four groups of 5 rats each: a normal diet group (control), a HCD group, and two groups of HCD with a daily dose of undigested muscle (Und) or the hydrolysate (MH) at 0.7 g kg⁻¹ of body weight. All animals received their respective treatments daily for 1 month. After the treatment period, serum lipid profiles, the activities of alanine aminotransferase and aspartate aminotransferase, the level of malonaldehyde, the activities of antioxidant enzymes (catalase and glutathione peroxidase) in the liver and sperm fertility parameters (in the epididymis and testis) were determined. Compared with those fed a standard diet, HCD induced dyslipidemia and oxidative stress, and decreased numerous reproductive parameters (mobility, count and viability). Interestingly, supplementing the HCD with thornback ray proteins attenuated all these anomalies, especially in the case where they were hydrolysed. These observations suggested that these proteins might contain bioactive peptides that possess hypocholesterolemic and antioxidant activities that ameliorate sperm damage.
This study was carried out to investigate the hypolipidemic, cardioprotective and anticoagulant properties of fish goby protein hydrolysates (GPHs) in rats fed a high fat and fructose diet (HFFD). Wistar rats were fed with HFFD for 2 months, coupled with the oral administration of GPHs and undigested goby protein (UGP). Compared with the standard diet, HFFD induced dyslipidemia and liver structure alterations, and increased pancreatic lipase activity. In addition, HFFD caused a significant increase in body weight. Interestingly, administration of UGP and GPHs to HFFD fed rats was efficacious in lowering serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-c) as well as hepatic TC and TG, and increased the serum high density lipoprotein cholesterol (HDL-c) content. Moreover, all treatments significantly decreased the atherogenic index and coagulant factor levels (thrombin and prothrombin). UGP and GPH administration also significantly decreased pancreatic lipase activity, which mitigates lipid accumulation. Similarly, UGP and its hydrolysates showed cardioprotective potential revealed by decreasing the risk of atherogenic and coronary artery disease and improving the liver architecture. The ex vivo plasma clotting test showed that GPHs exert a great therapeutic anticoagulant potential. The overall results demonstrated that GPH supplementation can counteract high-fat/fructose diet-induced obesity.
Living cells obtain energy either by oxidizing reduced compounds of organic or mineral origin or by absorbing light. Whichever energy source is used, some of the energy released is conserved by converting adenosine diphosphate (ADP) to adenosine triphosphate (ATP), which are analogous to the chemicals in a rechargeable battery. The energy released by the conversion of ATP back to ADP is used to drive most energy-requiring processes, including cell growth, cell division, communication and movement. It is clearly essential to life that the production and consumption of ATP are always maintained in balance, and the AMP-activated protein kinase (AMPK) is one of the key cellular regulatory systems that ensures this. In eukaryotic cells (cells with nuclei and other internal membrane-bound structures, including human cells), most ATP is produced in mitochondria, which are thought to have been derived by the engulfment of oxidative bacteria by a host cell not previously able to use molecular oxygen. AMPK is activated by increasing AMP or ADP (AMP being generated from ADP whenever ADP rises) coupled with falling ATP. Relatives of AMPK are found in essentially all eukaryotes, and it may have evolved to allow the host cell to monitor the output of the newly acquired mitochondria and step their ATP production up or down according to the demand. Structural studies have illuminated how AMPK achieves the task of detecting small changes in AMP and ADP, despite the presence of much higher concentrations of ATP. Recently, it has been shown that AMPK can also sense the availability of glucose, the primary carbon source for most eukaryotic cells, via a mechanism independent of changes in AMP or ADP. Once activated by energy imbalance or glucose lack, AMPK modifies many target proteins by transferring phosphate groups to them from ATP. By this means, numerous ATP-producing processes are switched on (including the production of new mitochondria) and ATP-consuming processes are switched off, thus restoring energy homeostasis. Drugs that modulate AMPK have great potential in the treatment of metabolic disorders such as obesity and Type 2 diabetes, and even cancer. Indeed, some existing drugs such as metformin and aspirin, which were derived from traditional herbal remedies, appear to work, in part, by activating AMPK.
Adipose tissue inflammation, characterized by augmented infiltration and altered polarization of macrophages, contributes to insulin resistance and its associated metabolic diseases. The NAD(+)-dependent deacetylase SIRT1 serves as a guardian against metabolic disorders in multiple tissues. To dissect the roles of SIRT1 in adipose tissues, metabolic phenotypes of mice with selective ablation of SIRT1 in adipocytes and myeloid cells were monitored. Compared to myeloid-specific SIRT1 depletion, mice with adipocyte-selective deletion of SIRT1 are more susceptible to diet-induced insulin resistance. The phenotypic changes in adipocyte-selective SIRT1 knockout mice are associated with an increased number of adipose-resident macrophages and their polarization toward the pro-inflammatory M1 subtype. Mechanistically, SIRT1 in adipocytes modulates expression and secretion of several adipokines, including adiponectin, MCP-1, and interleukin 4, which in turn alters recruitment and polarization of the macrophages in adipose tissues. In adipocytes, SIRT1 deacetylates the transcription factor NFATc1 and thereby enhances the binding of NFATc1 to the Il4 gene promoter. These findings suggest that adipocyte SIRT1 controls systemic glucose homeostasis and insulin sensitivity via the cross talk with adipose-resident macrophages.
Obesity has become a major threat to public health and is accompanied by chronic low-grade inflammation, which leads to various pathological developments. Lunasin, a natural seed peptide, exhibits several biological activities, such as anti-carcinogenesis, anti-inflammatory, and antioxidant activities. However, the mechanism of action of lunasin in obesity-related inflammation has not been investigated. The aim of this study was to explore whether lunasin could reduce the inflammation induced by obesity-related mediators in RAW264.7 cells and 3T3-L1 adipocytes and whether it could attenuate the crosstalk between the two cell lines. RAW264.7 cells were cultured in leptin-containing medium, adipocyte-conditioned medium (Ad-CM), or co-cultured with 3T3-L1 cells to mimic the physiology of obesity. The data showed that the secretion of pro-inflammatory cytokine interleukin-1β (IL-1β) was inhibited by lunasin after leptin activation of RAW264.7 cells. In addition, lunasin decreased monocyte chemoattractant protein-1 (MCP-1) and IL-1β secretions in the Ad-CM model. Cytokine MCP-1, IL-6, tumor necrosis factor (TNF)-α, and IL-1β secretions were significantly decreased by leptin or Ad-CM plus lipopolysaccharide stimulation. Subsequently, the co-culture of the two cells refined the direct relation between them, resulting in apparently increased MCP-1, and decreased IL-6 levels after lunasin treatment. In 3T3-L1 adipocytes, lunasin also exhibited anti-inflammatory property by inhibiting MCP-1, plasminogen activator inhibitor-1, and leptin productions stimulated by (TNF)-α, lipopolysaccharide, or RAW264.7 cell-conditioned medium. This result revealed that lunasin acts as a potential anti-inflammatory agent not only in macrophages but also in adipocytes, disrupting the crosstalk between these two cells. Therefore, this study suggests the intake of lunasin from diet or as a supplement, for auxiliary prevention or therapy in obesity-related inflammatory applications.
Brown algae and its carotenoids have been shown to have a positive influence on obesity and its comorbidities. This study evaluated the effect of Undaria pinnatifida and fucoxanthin on biochemical, physiological and inflammation markers related to obesity and on the expression of genes engaged on white adipose tissue lipid metabolism in a murine model of diet-induced obesity. The treatments improved energy expenditure, β-oxidation and adipogenesis by upregulating PPARα, PGC1α, PPARγ and UCP-1. Adipogenesis was also confirmed by image analysis of the retroperitoneal adipose tissue, by measuring cell area, perimeter and cellular density. Additionally, the treatments, ameliorated adipose tissue accumulation, insulin resistance, blood pressure, cholesterol and triglycerides concentration in serum, and reduced lipogenesis and inflammation by downregulating acetyl-CoA carboxylase (ACC) gene expression, increasing serum concentration and expression of adiponectin as well as downregulating IL-6 expression. Both fucoxanthin and Undaria pinnatifida may be considered for treating obesity and other diseases related.
Immune cell infiltration in (white) adipose tissue (AT) during obesity is associated with the development of insulin resistance. In AT, the main population of leukocytes are macrophages. Macrophages can be classified into two major populations: M1, classically activated macrophages, and M2, alternatively activated macrophages, although recent studies have identified a broad range of macrophage subsets. During obesity, AT M1 macrophage numbers increase and correlate with AT inflammation and insulin resistance. Upon activation, pro-inflammatory M1 macrophages induce aerobic glycolysis. By contrast, in lean humans and mice, the number of M2 macrophages predominates. M2 macrophages secrete anti-inflammatory cytokines and utilize oxidative metabolism to maintain AT homeostasis. Here, we review the immunologic and metabolic functions of AT macrophages and their different facets in obesity and the metabolic syndrome.
Obese postmenopausal women have an increased breast cancer risk, the principal mechanism for which is elevated estrogen production by adipose tissue; also, regardless of menstrual status and tumor estrogen dependence, obesity is associated with biologically aggressive breast cancers. Type 2 diabetes has a complex relationship with breast cancer risk and outcome; coexisting obesity may be a major factor, but insulin itself induces adipose aromatase activity and estrogen production and also directly stimulates breast cancer cell growth and invasion. Adipose tissue inflammation occurs frequently in obesity and type 2 diabetes, and proinflammatory cytokines and prostaglandin E2 produced by cyclooxygenase-2 in the associated infiltrating macrophages also induce elevated aromatase expression. In animal models, the same proinflammatory mediators, and the chemokine monocyte chemoattractant protein-1, also stimulate tumor cell proliferation and invasion directly and promote tumor-related angiogenesis. We postulate that chronic adipose tissue inflammation, rather than body mass index-defined obesity per se, is associated with an increased risk of type 2 diabetes and postmenopausal estrogen-dependent breast cancer. Also, notably before the menopause, obesity and type 2 diabetes, or perhaps the associated inflammation, promote estrogen-independent, notably triple-negative, breast cancer development, invasion and metastasis by mechanisms that may involve macrophage-secreted cytokines, adipokines and insulin.
Diabetes and obesity are worldwide health problems. White fat dynamically participates in hormonal and inflammatory regulation. White adipose tissue is recognized as a multifactorial organ that secretes several adipose-derived factors that have been collectively termed " adipokines. " Adipokines are pleiotropic molecules that gather factors such as leptin, adiponectin, visfatin, apelin, vaspin, hepcidin, RBP4, and inflammatory cytokines, including TNF and IL-1í µí»½, among others. Multiple roles in metabolic and inflammatory responses have been assigned to these molecules. Several adipokines contribute to the self-styled " low-grade inflammatory state " of obese and insulin-resistant subjects, inducing the accumulation of metabolic anomalies within these individuals, including autoimmune and inflammatory diseases. Thus, adipokines are an interesting drug target to treat autoimmune diseases, obesity, insulin resistance, and adipose tissue inflammation. The aim of this review is to present an overview of the roles of adipokines in different immune and nonimmune cells, which will contribute to diabetes as well as to adipose tissue inflammation and insulin resistance development. We describe how adipokines regulate inflammation in these diseases and their therapeutic implications. We also survey current attempts to exploit adipokines for clinical applications, which hold potential as novel approaches to drug development in several immune-mediated diseases.
Recently, obesity has increased due to a variety of reasons, including the availability of 'fast food' and high-fat diets. Developing anti-obesity functional drugs and foods from natural sources may offer solutions to this global concern. Generally, tuna is a high-protein, low-fat and low-calorie food with various bioactive effects. It may improve memory, reduce cholesterol levels and positively affect the development of brain cells. In this study, we screened the anti-obesity potential of peptides derived from tuna protein. We then observed protein bands by the Coomassie blue staining of a sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gel. The protein mixture was concentrated and desalted using in-gel trypsin digestion and a C18 nano column and Poros R2 reversed-phase preparation, prior to quadrupole time-of-flight mass spectrometry (Q-TOF MS/MS). We screened the peptides for their ability to affect adipogenesis in 3T3-L1 adipocytes. We also measured glucose uptake, triglyceride levels and lipid droplets using Oil Red O staining. As a result, we confirmed that one peptide inhibited adipocyte differentiation. We also observed the expression of obesity-related genes by western blot analysis and reverse transcription-polymerase chain reaction. The peptide from the tuna extract significantly reduced the expression levels of CCAAT/enhancer-binding protein α (C/EBP-α) and peroxisome proliferator-activated receptor-γ (PPAR-γ) adipocyte marker genes. Thus, our data suggest that this peptide from boiled tuna extract reduces lipid components and adipogenesis in 3T3-L1 cells, and these characteristics may be of value in the development of anti-obesity foods.
Adipose tissue is a complex, multicellular organ that profoundly influences the function of nearly all other organ systems through its diverse metabolite and adipokine secretome. Adipocytes are the primary cell type of adipose tissue and play a key role in maintaining energy homeostasis. The efficiency with which adipose tissue responds to whole-body energetic demands reflects the ability of adipocytes to adapt to an altered nutrient environment, and has profound systemic implications. Deciphering adipocyte cell biology is an important component of understanding how the aberrant physiology of expanding adipose tissue contributes to the metabolic dysregulation associated with obesity.
© 2015 Rutkowski et al.
Milk derived tripeptides IPP (Ile-Pro-Pro) and VPP (Val-Pro-Pro) have shown promise as anti-hypertensive agents due to their inhibitory effects on angiotensin converting enzyme (ACE). Due to the key inter-related roles of hypertension, chronic inflammation and insulin resistance in the pathogenesis of metabolic syndrome, there is growing interest in investigating established anti-hypertensive agents for their effects on insulin sensitivity and inflammation. In this study, we examined the effects of IPP and VPP on 3T3-F442A murine pre-adipocytes, a widely used model for studying metabolic diseases. We found that both IPP and VPP induced beneficial adipogenic differentiation as manifested by intracellular lipid accumulation, upregulation of peroxisome proliferator-activated receptor gamma (PPARγ) and secretion of the protective lipid hormone adiponectin by these cells. The observed effects were similar to those induced by insulin, suggesting potential benefits in the presence of insulin resistance. IPP and VPP also inhibited cytokine induced pro-inflammatory changes such as reduction in adipokine levels and activation of the nuclear factor kappa B (NF-κB) pathway. Taken together, our findings suggest that IPP and VPP exert insulin-mimetic adipogenic effects and prevent inflammatory changes in adipocytes, which may offer protection against metabolic disease.
Sirtuins (SIRTs) are master metabolic regulators with protective roles against obesity and obesity-associated metabolic disorders, including non-alcoholic fatty liver disease (NAFLD) and type-2 diabetes. We aimed to ascertain whether there is a relationship between serum SIRT1 and liver steatosis severity in obese patients. Seventy-two obese patients (BMI ≥ 30 kg/m(2)), 18 males and 54 females, mean age 39.66 ± 12.34 years, with ultrasonographic evidence of NAFLD, were studied. BMI, transaminases, insulin, HOMA-index, HbA1c, body composition (DXA), plasma SIRT1 levels (ELISA) and representative measures of metabolic syndrome (waist circumference, fasting plasma glucose, blood pressure, HDL-cholesterol, triglycerides) and inflammation (ESR, CRP, fibrinogen) were evaluated. Thirty healthy lean patients were included as controls. SIRT1 was significantly lower in severe liver steatosis obese group compared to the mild steatosis group, both had lower SIRT1 plasma values compared to control lean patients (P = 0.0001). SIRT1 showed an inverse correlation with liver steatosis and HbA1c in univariate analysis (ρ = -0.386; P = 0.001; ρ = -0.300; P = 0.01, respectively). Multiple linear regression analysis showed that liver steatosis was the independent correlate of SIRT1 even after adjustment for potentially relevant variables (β = -0.442; P = 0.003). Serum SIRT1 might be a novel clinical/biochemical parameter associated with fat liver infiltration. Further studies in larger cohorts are warranted.
Acute kidney injury (AKI) is a common complication of critical illness, and evidence is emerging that suggests AKI disrupts the function of other organs. It is a recognized phenomenon that patients with chronic kidney disease (CKD) have reduced hepatic metabolism of drugs, via the cytochrome P450 (CYP) enzyme group, and drug dosing guidelines in AKI are often extrapolated from data obtained from patients with CKD. This approach, however, is flawed because several confounding factors exist in AKI. The data from animal studies investigating the effects of AKI on CYP activity are conflicting, although the results of the majority do suggest that AKI impairs hepatic CYP activity. More recently, human study data have also demonstrated decreased CYP activity associated with AKI, in particular the CYP3A subtypes. Furthermore, preliminary data suggest that patients expressing the functional allele variant CYP3A5*1 may be protected from the deleterious effects of AKI when compared with patients homozygous for the variant CYP3A5*3, which codes for a non-functional protein. In conclusion, there is a need to individualize drug prescribing, particularly for the more sick and vulnerable patients, but this needs to be explored in greater depth.
Adipocyte differentiation and function have become areas of intense focus in the field of energy metabolism; however, understanding the role of specific genes inthe establishment and maintenance of fat cell function can be challenging and complex. In this review, we offer practical guidelines for the study of adipocyte development and function. We discuss improved cellular and genetic systems for the study of adipose biology and highlight recent insights gained from these new approaches. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.
This work determined the ability of hemp seed meal protein hydrolysate (HMH)-containing diets to attenuate elevated blood pressure (hypertension) development in spontaneously hypertensive rats (SHRs). Effects of diets on plasma levels of renin and angiotensin I-converting enzyme (ACE) in the SHRs were also determined.
Defatted hemp seed protein meal was hydrolyzed using simulated gastrointestinal tract digestion with pepsin followed by pancreatin, and the resulting HMH used as a source of antihypertensive peptides. The HMH was substituted for casein at 0.5 and 1.0 % levels and fed to young growing rats for 8 weeks (preventive phase) or adult rats for 4 weeks (treatment phase).
Feeding of young growing SHRs with HMH resulted in attenuation of the normal increases in systolic blood pressure (SBP) with an average value of ~120 mmHg when compared to the casein-only group of rats (control) with a maximum of 158 mm Hg (p < 0.05). Feeding adult rats (SBP ~145 mmHg) with same diets during a 4-week period led to significant (p < 0.05) reduction in SBP to ~119 mmHg in comparison with 150 mmHg for the control rats. Plasma ACE activity was significantly (p < 0.05) suppressed (0.047-0.059 U/mL) in HMH-fed rats when compared to control rats (0.123 U/mL). Plasma renin level was also decreased for HMH-fed rats (0.040-0.054 μg/mL) when compared to control rats that were fed only with casein (0.151 μg/mL).
The results suggest that HMH with strong hypotensive effects in SHRs could be used as a therapeutic agent for both the prevention and treatment of hypertension.
The chemokine CCL2, which is best known for its chemotactic functions, is expressed not only by immune cells, but also by several types of malignant and stromal cells. CCL2 has been shown to exert both pro- and anti-tumor effects. However, recent results demonstrate a main role for CCL2 in tumor progression and metastasis, suggesting that this chemokine may constitute a therapeutic target for anticancer drugs. Mammary carcinoma models, including models of implantable, transgenic, and chemically-induced tumors, were employed in the setting of Ccl2 or Ccr2 knockout mice or CCL2 neutralization with a monoclonal antibody to further investigate the role of the CCL2/CCR2 signaling axis in tumor progression and metastatic spread. In our implantable tumor models, an anti-CCL2 monoclonal antibody inhibited the growth of primary malignant lesions in a biphasic manner and reduced the number of metastases. However, in Ccl2(-/-) or Ccr2(-/-) mice developing implanted or transgenic tumors, the number of pulmonary metastases was increased despite a reduction in the growth rate of primary neoplasms. Transgenic Mtag.Ccl2(-/-) or Mtag.Ccr2(-/-) mice also exhibited a significantly earlier of disease onset. In a chemical carcinogenesis model, anti-CCL2 monoclonal antibody inhibited the growth of established lesions but was ineffective in the tumor induction phase. In contrast to previous studies indicating a role for CCL2 in the establishment of metastases, we have demonstrated that the absence of CCL2/CCR2-signaling results in increased metastatic disease. Thus, the CCL2/CCR2 signaling axis appears to play a dual role in mediating early tumor immunosurveillance and sustaining the growth and progression of established neoplasms. Our findings support the use of anti-CCL2 therapies for the treatment of established breast carcinoma, although the complete abrogation of the CCL2 signaling cascade may also limit immunosurveillance and support metastatic spread.
The number of cancer cases caused by being obese is estimated to be 20% with the increased risk of malignancies being influenced by diet, weight change, and body fat distribution together with physical activity. Reports from the International Agency for Research into Cancer and the World Cancer Research Fund (WCRF) have shown that the strongest evidence exists for an association of obesity with the following cancer types: endometrial, esophageal adenocarcinoma, colorectal, postmenopausal breast, prostate, and renal, whereas the less common malignancies are leukemia, non-Hodgkin's lymphoma, multiple myeloma, malignant melanoma, and thyroid tumours. To be able to develop novel methods in prevention and treatment, we first must understand the underlying processes which link cancer to obesity. Four main systems have been identified as potential producers of cancer in obesity: insulin, insulin-like growth factor-I, sex steroids, and adipokines. Various novel candidate mechanisms have been proposed: chronic inflammation, oxidative stress, crosstalk between tumour cells and surrounding adipocytes, migrating adipose stromal cells, obesity-induced hypoxia, shared genetic susceptibility, and the functional defeat of immune function. Herein, we review the major pathogenic links between obesity and susceptibility to cancer.
Peroxisome proliferator-activated receptor a (PPARa) plays a key role in the transcriptional control of genes encoding mitochondrial fatty acid b-oxidation (FAO) enzymes. In this study we sought to determine whether the recently identified PPAR gamma coactivator 1 (PGC-1) is capable of coactivating PPARa in the transcriptional control of genes encoding FAO enzymes. Mammalian cell cotransfection experiments demon- strated that PGC-1 enhanced PPARa-mediated transcriptional activation of reporter plasmids containing PPARa target elements. PGC-1 also enhanced the transactivation activity of a PPARa-Gal4 DNA binding domain fusion protein. Retroviral vector-mediated expression studies performed in 3T3-L1 cells demonstrated that PPARa and PGC-1 cooperatively induced the expression of PPARa target genes and increased cellular palmitate oxidation rates. Glutathione S-transferase "pulldown" studies revealed that in contrast to the previously reported ligand-independent interaction with PPARg, PGC-1 binds PPARa in a ligand-influenced manner. Protein-protein interaction studies and mammalian cell hybrid experiments demonstrated that the PGC-1-PPARa interaction involves an LXXLL domain in PGC-1 and the PPARa AF2 region, consistent with the observed ligand influence. Last, the PGC-1 transactivation domain was mapped to within the NH2-terminal 120 amino acids of the PGC-1 molecule, a region distinct from the PPARa interacting domains. These results identify PGC-1 as a coactivator of PPARa in the transcriptional control of mitochondrial FAO capacity, define separable PPARa interaction and transactivation domains within the PGC-1 molecule, and demonstrate that certain features of the PPARa-PGC-1 interaction are distinct from that of PPARg-PGC-1.
In a state of caloric excess, adipose tissue plays an essential role by storing lipids. Its expandability determines the onset of metabolic syndrome (central obesity, dyslipidemia, glucose intolerance and hypertension). When the adipocyte endoplasmic reticulum is no longer capable of processing the excess nutrients, the so-called "endoplasmic reticulum stress" develops. This triggers efflux of free fatty acids from adipocytes into the circulation and causes triglyceride overload in skeletal muscle, liver and pancreas. Adipose tissue hypoxia then develops, due to the failure of vasculature to expand with adipocyte hypertrophy. Increased catabolism in mitochondria leads there to oxidative stress. Both phenomena cause deranged adipokine secretion and low-grade inflammation. Inflammatory cytokines, reactive oxygen species and ectopic lipid deposition are the main mediators of insulin resistance and vascular impairment, which both lead finally to diabetes type 2 and cardiovascular disease. Recently, fibrosis of adipose tissue was also demonstrated in obesity, contributing to the interplay of deleterious factors forcing inflammation. The present paper reviews recent evidence for adipose tissue dysfunction, trying to define causes and consequences. In conclusion, insulin resistance and associated complications originate from excess lipids, which cannot be stored without limit in adipose tissue, thus affecting its integrity and adipokine secretion.
AMPK has emerged as a critical mechanism for salutary effects of polyphenols on lipid metabolic disorders in type 1 and type 2 diabetes. Here we demonstrate that AMPK interacts with and directly phosphorylates sterol regulatory element binding proteins (SREBP-1c and -2). Ser372 phosphorylation of SREBP-1c by AMPK is necessary for inhibition of proteolytic processing and transcriptional activity of SREBP-1c in response to polyphenols and metformin. AMPK stimulates Ser372 phosphorylation, suppresses SREBP-1c cleavage and nuclear translocation, and represses SREBP-1c target gene expression in hepatocytes exposed to high glucose, leading to reduced lipogenesis and lipid accumulation. Hepatic activation of AMPK by the synthetic polyphenol S17834 protects against hepatic steatosis, hyperlipidemia, and accelerated atherosclerosis in diet-induced insulin-resistant LDL receptor-deficient mice in part through phosphorylation of SREBP-1c Ser372 and suppression of SREBP-1c- and -2-dependent lipogenesis. AMPK-dependent phosphorylation of SREBP may offer therapeutic strategies to combat insulin resistance, dyslipidemia, and atherosclerosis.
Lipolysis is the biochemical pathway responsible for the catabolism of triacylglycerol (TAG) stored in cellular lipid droplets. The hydrolytic cleavage of TAG generates non-esterified fatty acids, which are subsequently used as energy substrates, essential precursors for lipid and membrane synthesis, or mediators in cell signaling processes. Consistent with its central importance in lipid and energy homeostasis, lipolysis occurs in essentially all tissues and cell types, it is most abundant, however, in white and brown adipose tissue. Over the last 5years, important enzymes and regulatory protein factors involved in lipolysis have been identified. These include an essential TAG hydrolase named adipose triglyceride lipase (ATGL) [annotated as patatin-like phospholipase domain-containing protein A2], the ATGL activator comparative gene identification-58 [annotated as α/β hydrolase containing protein 5], and the ATGL inhibitor G0/G1 switch gene 2. Together with the established hormone-sensitive lipase [annotated as lipase E] and monoglyceride lipase, these proteins constitute the basic "lipolytic machinery". Additionally, a large number of hormonal signaling pathways and lipid droplet-associated protein factors regulate substrate access and the activity of the "lipolysome". This review summarizes the current knowledge concerning the enzymes and regulatory processes governing lipolysis of fat stores in adipose and non-adipose tissues. Special emphasis will be given to ATGL, its regulation, and physiological function.
PPARgamma activation in type 2 diabetic patients results in a marked improvement in insulin and glucose parameters, resulting from an improvement of whole-body insulin sensitivity. Adipose tissue is the major mediator of PPARgamma action on insulin sensitivity. PPARgamma activation in mature adipocytes induces the expression of a number of genes involved in the insulin signaling cascade, thereby improving insulin sensitivity. PPARgamma is the master regulator of adipogenesis, thereby stimulating the production of small insulin-sensitive adipocytes. In addition to its importance in adipogenesis, PPARgamma plays an important role in regulating lipid, metabolism in mature adipocytes by increasing fatty acid trapping. Finally, adipose tissue produces several cytokines that regulate energy homeostasis, lipid and glucose metabolism. Disturbances in the production of these factors may contribute to metabolic abnormalities, and PPARgamma activation is also associated with beneficial effects on expression and secretion of a whole range of cytokines.
Hepatic insulin resistance plays a vital role in the development of type 2 diabetes. In the current study, the reduction effects of casein glycomacropeptide hydrolysates obtained with papain (GHP) on hepatic insulin resistance were investigated in high-fat diet (HFD)-fed C57BL/6J mice. Mice were fed with HFD for 8 weeks and then gavaged with GHP at doses of 100, 200 and 400 mg/kg body weight daily for another 8 weeks while continuing with HFD feeding. Results showed that GHP significantly decreased the levels of fasting blood glucose and serum insulin, and homeostasis model of insulin resistance index in HFD mice. The glucose tolerance and hepatic glycogen content were increased by GHP treatment in HFD mice. Besides, the hepatic steatosis and macrophages infiltration were ameliorated by GHP in HFD mice. Furthermore, GHP reduced the serine phosphorylation of IRS-1 and elevated Akt phosphorylation, which increased GSK3β phosphorylation in liver tissue of HFD mice. The decreased hepatic AMPK phosphorylation and increased hepatic MAPK phosphorylation induced by HFD were reversed by GHP, which contributed to the restoration of hepatic insulin sensitivity, reduction of hepatic steatosis and macrophage infiltration. Thus, GHP supplementation may be an alternative therapeutic approach against hepatic insulin resistance.
Bioactive peptides have many structural features that enable them to become functional in controlling several biological processes in the body, especially those related to metabolic health. This chapter provides an overview of the multiple targets of food-derived peptides against metabolic health problems (e.g., hypertension, dyslipidemia, hyperglycemia, oxidative stress) and discusses the importance of structural chemistry in determining the bioactivities of peptides and protein hydrolysates.
Aims:
Activation of the NAD(+) dependent protein deacetylase SIRT1 has been proposed as a therapeutic strategy to treat mitochondrial dysfunction and insulin resistance in skeletal muscle. However, life-long overexpression of SIRT1 in skeletal muscle does not improve parameters of mitochondrial function and insulin sensitivity. In this study we investigated whether temporal overexpression of SIRT1 in muscle of adult mice would affect skeletal muscle mitochondrial function and insulin sensitivity.
Methods:
To circumvent potential effects of germline SIRT1 overexpression, we utilized an inducible model of SIRT1 overexpression in skeletal muscle of adult mice (i-mOX). Insulin sensitivity was assessed by 2-deoxyglucose uptake, muscle maximal respiratory function by high-resolution respirometry and systemic energy expenditure was assessed by whole body calorimetry.
Results:
Although SIRT1 was highly, and specifically, overexpressed in skeletal muscle of i-mOX compared to WT mice, glucose tolerance and skeletal muscle insulin sensitivity were comparable between genotypes. Additionally, markers of mitochondrial biogenesis, muscle maximal respiratory function and whole body oxygen consumption were also unaffected by SIRT1 overexpression.
Conclusion:
These results support previous work demonstrating that induction of SIRT1 in skeletal muscle, either at birth or in adulthood, does not impact muscle insulin action or mitochondrial function. This article is protected by copyright. All rights reserved.
Background:
Little is known about the effects of cocoa and its main flavanols on the prothrombotic state associated with the development of hypertension in diet-induced obesity models.
Purpose:
To evaluate the effects of cocoa powder, cocoa extract and their main flavanols on plasma biomarkers related to impaired coagulation and fibrinolysis and its association with hypertension and obesity-related metabolic disorders in rats fed a hypercaloric diet.
Methods:
Male Wistar rats were randomly assigned to 7 treatment groups (n = 7): normal diet (ND); hypercaloric diet control group (HCD); HCD + cocoa powder (CO); HCD + cocoa extract (CO-EX); HCD + (-)-epicatechin (EPI); HCD + (+)-catechin (CAT); and HCD + procyanidin B2 (PB2). Blood pressure was measured using the tail-cuff method (week 7). At the end of the experimental period (week 8), rats were sacrificed and blood samples were collected immediately for coagulation and biochemical analyses.
Results:
Oral administration of CO, CO-EX and their main flavanols significantly decreased plasma biomarkers related to impaired coagulation and fibrinolysis (vWF, FVIII, fibrinogen and PAI-1) in rats fed a hypercaloric diet. These effects were associated with decreased systolic and diastolic blood pressure, aortic oxidative stress (MDA levels) and improvement of dyslipidemia, insulin resistance and circulating markers of inflammation (TNF-α, IL-6 and CRP) compared to the HCD group.
Conclusion:
Our results showed that cocoa and its main flavanols may improve endothelial dysfunction and exert their antihypertensive effects by decreasing the prothrombotic state in rats fed a hypercaloric diet. Moreover, improvement of obesity-related metabolic disorders may also contribute to their BP-lowering effect.
Cocoa flavan-3-ols have been shown to exert a positive influence on obesity-related metabolic risk factors. This study evaluated the effects of cocoa powder (Co), cocoa extract (Co-Ex) and its main flavanols (Epi, Cat and PB2) on the expression of genes involved in WAT lipid metabolism in a rat model of hypercaloric diet-induced obesity. Co, Co-Ex and Epi are associated with adipogenesis, β-oxidation and energy expenditure in WAT linked to upregulating the expression of peroxisome-proliferator-activated receptor γ (PPARγ), PPARα, PPARγ coactivator 1α (PGC1α), sirtuin 1 (SIRT1) and uncoupling protein 1 (UCP1). Additionally, these treatments are associated with decreases in body weight gain and total fat mass and insulin resistance, reduced lipogenesis, and inflammation related to downregulating acetyl-CoA carboxylase gene expression, decreasing TNF-α and increasing ApN concentrations in WAT. Co, Co-Ex and Epi may be considered to be potential agents for the treatment of obesity-related metabolic disorders.
Bioactive peptides are encrypted within the primary structure of food proteins where they remain inactive until released by enzymatic hydrolysis. Once released from the parent protein, certain peptides have the ability to modulate the renin-angiotensin system (RAS) because they decrease activities of renin or angiotensin-converting enzyme (ACE), the two main enzymes that regulate mammalian blood pressure. These antihypertensive peptides can also enhance the endothelial nitric oxide synthase (eNOS) pathway to increase nitric oxide (NO) levels within vascular walls and promote vasodilation. The peptides can block the interactions between angiotensin II (vasoconstrictor) and angiotensin receptors, which can contribute to reduced blood pressure. This review focuses on the methods that are involved in antihypertensive peptide production from food sources, including fractionation protocols that are used to enrich bioactive peptide content and enhance peptide activity. It also discusses mechanisms that are believed to be involved in the antihypertensive activity of these peptides.
Chronic hyperglycemia in diabetes is associated with oxidative stress-mediated tissue damage. The present study is aimed to explore the role of a cocoa-enriched diet in ameliorating the oxidative stress-induced damage in the liver of young type 2 diabetic Zucker Diabetic fatty (ZDF) rats. Male ZDF rats were fed a control or cocoa-rich diet (10%), and Zucker Lean (ZL) animals received the control diet. ZDF rats fed with cocoa (ZDF-Ca) decreased body weight gain, glucose and insulin levels, and improved glucose tolerance and insulin resistance. Cocoa diet further reduced reactive oxygen species (ROS) levels and carbonyl content in the liver of ZDF animals. The diminished activity of superoxide dismutase (SOD) and the enhanced activity of heme oxygenase (HO-1) in ZDF-C were returned to ZL values upon cocoa administration. Cocoa did not restore the decreased glutathione-S-transferase (GST) activity in both ZDF groups in comparison to ZL rats. Glutathione (GSH) content and activities of glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) remained unaltered among all animal groups. Moreover, cocoa-rich diet suppressed total and phosphorylated nuclear factor erythroid-derived 2-like 2 (Nrf2), as well as p65-nuclear factor-kappaB (NF-ĸB) enhanced levels observed in ZDF rats. The results indicate that cocoa protects the hepatocytes by improving the antioxidant competence in the liver of young type 2 diabetic ZDF rats.
Chronic, low-grade adipose tissue inflammation is a key etiological mechanism linking the increasing incidence of type 2 diabetes (T2D) and obesity. It is well recognized that the immune system and metabolism are highly integrated, and macrophages, in particular, have been identified as critical effector cells in the initiation of inflammation and insulin resistance. Recent advances have been made in the understanding of macrophage recruitment and retention to adipose tissue and the participation of other immune cell populations in the regulation of this inflammatory process. Here we discuss the pathophysiological link between macrophages, obesity, and insulin resistance, highlighting the dynamic immune cell regulation of adipose tissue inflammation. We also describe the mechanisms by which inflammation causes insulin resistance and the new therapeutic targets that have emerged.
In diet-induced obesity, adipose tissue (AT) is in a chronic state of inflammation predisposing the development of metabolic syndrome. Cocoa (Theobroma cacao) is a polyphenol-rich food with putative anti-inflammatory activities. Here, we examined the impact and underlying mechanisms of action of cocoa on AT inflammation in high fat-fed mice. In the present study, male C57BL/6 J mice were fed a high fat diet (HF), a HF diet with 8% (w/w) unsweetened cocoa powder (HFC), or a low-fat diet (LF) for 18 wk. Cocoa supplementation decreased AT mRNA levels of tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase, and EGF-like module-containing mucin-like hormone receptor-like 1 by 40 – 60% compared to HF group, and this was accompanied by decreased nuclear protein levels of nuclear factor-κB. Cocoa treatment reduced the levels of arachidonic acid in the AT by 33% compared to HF controls. Moreover, cocoa treatment also reduced protein levels of the eicosanoid-generating enzymes, adipose-specific phospholipase A2 and cycloxygenase-2 by 53% and 55%, respectively, compared to HF-fed mice. Finally, cocoa treatment ameliorated metabolic endotoxemia (40% reduction in plasma endotoxin) and improved gut barrier function (as measured by increased plasma levels of glucagon-like peptide-2). In conclusion, the present study has shown for the first time that long-term cocoa supplementation can reduce AT inflammation in part by modulating eicosanoid metabolism and metabolic endotoxemia.
Initially known as multiple system organ failure, the term multiple organ dysfunction syndrome (MODS) was first described in the 1960s in adults with bleeding, respiratory failure, and sepsis. It is defined as "the development of potentially reversible physiologic derangement involving two or more organ systems not involved in the disorder that resulted in ICU admission, and arising in the wake of a potentially life threatening physiologic insult."(3) There are many risk factors predisposing to MODS; however, the most common risk factors are shock due to any cause, sepsis, and tissue hypoperfusion. A dysregulated immune response, or immuneparalysis, in which the homeostasis between pro-inflammatory and anti-inflammatory reaction is lost is thought to be key in the development of MODS. The clinical course and evolution of MODS is dependent on a combination of acquired and genetic factors. There are several nonspecific therapies for the prevention and resolution of MODS, mostly care is supportive. Mortality from MODS in septic pediatric patients varies between 11% and 54%.
Obesity and related metabolic diseases (e.g., type 2 diabetes, cardiovascular diseases, and hypertension) are the most prevailing nutrition-related issues in the world. An emerging feature of obesity is their relationship with chronic inflammation that begins in white adipose tissue and eventually becomes systemic. One potential dietary strategy to reduce glucose intolerance and inflammation is consumption of polyphenol-rich cocoa-like cocoa or their by-products. In vitro as well as in vivo data indicate that cocoa polyphenols (CPs) may exhibit antioxidant and anti-inflammatory properties. Polyphenols commonly found in cocoa have been reported to regulate lipid metabolism via inducing metabolic gene expression or activating transcription factors that regulate the expression of numerous genes, many of which play an important role in energy metabolism. Currently, several molecular targets (e.g., nuclear factor Kappa B, activated protein-1, peroxisome proliferator-activated receptors, liver X receptors, and adiponectin gene) have been identified, which may explain potential beneficial obesity-associated diseases effects of CPs. Further studies have been performed regarding the protective effects of CPs against metabolic diseases by suppressing transcription factors that antagonize lipid accumulation. Thus, polyphenols-rich cocoa products may diminish obesity-mediated metabolic diseases by multiple mechanisms, thereby attenuating chronic inflammation.
Insulin resistance is a hallmark of obesity, the cardiorenal metabolic syndrome and type 2 diabetes mellitus (T2DM). The progression of insulin resistance increases the risk for cardiovascular disease (CVD). The significance of insulin resistance is underscored by the alarming rise in the prevalence of obesity and its associated comorbidities in the Unites States and worldwide over the last 40-50years. The incidence of obesity is also on the rise in adolescents. Furthermore, premenopausal women have lower CVD risk compared to men, but this protection is lost in the setting of obesity and insulin resistance. Although systemic and cardiovascular insulin resistance is associated with impaired insulin metabolic signaling and cardiovascular dysfunction, the mechanisms underlying insulin resistance and cardiovascular dysfunction remain poorly understood. Recent studies show that insulin resistance in obesity and diabetes is linked to a metabolic inflammatory response, a state of systemic and tissue specific chronic low grade inflammation. Evidence is also emerging that there is polarization of macrophages and lymphocytes towards a pro-inflammatory phenotype that contributes to progression of insulin resistance in obesity, cardiorenal metabolic syndrome and diabetes. In this review, we provide new insights into factors, such as, the renin-angiotensin-aldosterone system, sympathetic activation and incretin modulators (e.g., DPP-4) and immune responses that mediate this inflammatory state in obesity and other conditions characterized by insulin resistance.
Objective:
The scavenger receptor CD36 facilitates the cellular uptake of long-chain fatty acids. As CD36-deficiency attenuates the development of high fat diet (HFD)-induced obesity, the role of CD36-deficiency in preadipocyte recruitment and adipocyte function was set out to characterize.
Design and methods:
Fat cell size and number were determined in gonadal, visceral, and subcutaneous adipose tissue of CD36(-/-) and WT mice after 6 weeks on HFD. Basal lipolysis and insulin-inhibited lipolysis were investigated in gonadal adipose tissue.
Results:
CD36(-/-) mice showed a reduction in adipocyte size in all fat pads. Gonadal adipose tissue also showed a lower total number of adipocytes because of a lower number of very small adipocytes (diameter <50 μm). This was accompanied by an increased pool of preadipocytes, which suggests that CD36-deficiency reduces the capacity of preadipocytes to become adipocytes. Regarding lipolysis, in adipose tissue from CD36(-/-) mice, cAMP levels were increased and both basal and 8-bromo-cAMP stimulated lipolysis were higher. However, insulin-mediated inhibition of lipolysis was more potent in CD36(-/-) mice.
Conclusions:
These results indicate that during fat depot expansion, CD36-deficiency negatively affects preadipocyte recruitment and that in mature adipocytes, CD36-deficiency is associated with increased basal lipolysis and insulin responsiveness.
Purpose:
To investigate the effect of cocoa powder supplementation on obesity-related inflammation in high fat (HF)-fed obese mice.
Methods:
Male C57BL/6J (n = 126) were fed with either low-fat (LF, 10 % kcal from fat) or HF (60 % kcal from fat) diet for 18 weeks. After 8 weeks, mice from HF group were randomized to HF diet or HF diet supplemented with 8 % cocoa powder (HF-HFC group) for 10 weeks. Blood and tissue samples were collected for biochemical analyses.
Results:
Cocoa powder supplementation significantly reduced the rate of body weight gain (15.8 %) and increased fecal lipid content (55.2 %) compared to HF-fed control mice. Further, cocoa supplementation attenuated insulin resistance, as indicated by improved HOMA-IR, and reduced the severity of obesity-related fatty liver disease (decreased plasma alanine aminotransferase and liver triglyceride) compared to HF group. Cocoa supplementation also significantly decreased plasma levels of the pro-inflammatory mediators interleukin-6 (IL-6, 30.4 %), monocyte chemoattractant protein-1 (MCP-1, 25.2 %), and increased adiponectin (33.7 %) compared to HF-fed mice. Expression of pro-inflammatory genes (Il6, Il12b, Nos2, and Emr1) in the stromal vascular fraction (SVF) of the epididymal white adipose tissue (WAT) was significantly reduced (37-56 %) in the cocoa-supplemented mice.
Conclusions:
Dietary supplementation with cocoa ameliorates obesity-related inflammation, insulin resistance, and fatty liver disease in HF-fed obese mice, principally through the down-regulation of pro-inflammatory gene expression in WAT. These effects appear to be mediated in part by a modulation of dietary fat absorption and inhibition of macrophage infiltration in WAT.
Hyperlipidaemia is an important risk factor for developing cardiovascular disease, a leading global health issue. While pharmaceutical interventions have proved efficacious in acute conditions, many hypolipidaemic drugs are known to induce adverse side effects. Due to a strong positive link between functional food components and human health, emerging research has explored the application of natural food-based strategies in disease management. One of such strategies involves the use of food proteins as precursors of peptides with a wide variety of beneficial health functions. Some plant, animal and marine-derived protein hydrolysates and peptides have shown promising hypolipidaemic properties when evaluated in vitro, in cultured mammalian cells and animal models. The products exert their functions via bile acid-binding and disruption of cholesterol micelles in the gastrointestinal tract, and by altering hepatic and adipocytic enzyme activity and gene expression of lipogenic proteins, which can modulate aberrant physiological lipid profiles. The activity of the protein hydrolysates and peptides depends on their physicochemical properties including hydrophobicity of amino acid residues but there is knowledge gap on detailed structure-function relationships and efficacy in hyperlipidaemic human subjects. Based on the prospects, commercial functional food products containing hypolipidaemic peptides have been developed for enhancement of cardiovascular health.
Brown adipose tissue (BAT) can disperse stored energy as heat. Promoting BAT-like features in white adipose (WAT) is an attractive, if elusive, therapeutic approach to staunch the current obesity epidemic. Here we report that gain of function of the NAD-dependent deacetylase SirT1 or loss of function of its endogenous inhibitor Deleted in breast cancer-1 (Dbc1) promote "browning" of WAT by deacetylating peroxisome proliferator-activated receptor (Ppar)-γ on Lys268 and Lys293. SirT1-dependent deacetylation of Lys268 and Lys293 is required to recruit the BAT program coactivator Prdm16 to Pparγ, leading to selective induction of BAT genes and repression of visceral WAT genes associated with insulin resistance. An acetylation-defective Pparγ mutant induces a brown phenotype in white adipocytes, whereas an acetylated mimetic fails to induce "brown" genes but retains the ability to activate "white" genes. We propose that SirT1-dependent Pparγ deacetylation is a form of selective Pparγ modulation of potential therapeutic import.
Cocoa seeds and pulp were fermented for 144 h, followed by natural drying. The tegument was removed and the cotyledons were broken into nibs which were roasted at 150 °C for 30 min. Non-fermented material, material fermented for 24, 48 and 72 h, material fermented for 144 h and then dried, and also the roasted nibs, were all prepared for chemical and microscopic analyses. Light microscopy revealed the presence of anionic and cationic residues and of neutral sugars. During fermentation there was a reduction in the cytoplasmic content of phenolic compounds and in the number of protein bodies. The cell wall showed a reduction in anionic residues and a loss of crystallinity. These alterations were maximum after 72 h. Drying and roasting increased the number of damaged cells and reduced the amount of cytoplasmic material. The chemical analyses generally confirmed the microscopy results. The concentration of amino-terminal groups and total free amino acids increased during fermentation (up to 72 h), but returned to the initial values after roasting. The principal chemical changes were related to reducing sugars, free amino acids, proteins and phenols, and PCA was suggested as a useful tool to compare different samples. Microscopic analysis revealed the degradation of protein and phenolic bodies and cellular damage during roasting.© 2000 Society of Chemical Industry
Monocyte Chemoattractant Protein-1 (MCP-1) is the first discovered and most extensively studied CC chemokine, and the amount of studies on its role in the etiologies of obesity- and diabetes-related diseases have increased exponentially during the past two decades. This review attempted to provide a panoramic perspective of the history, regulatory mechanisms, functions, and therapeutic strategies of this chemokine. The highlights of this review include the roles of MCP-1 in the development of obesity, diabetes, cardiovascular diseases, insulitis, diabetic nephropathy, and diabetic retinopathy. Therapies that specifically or non-specifically inhibit MCP-1 overproduction have been summarized.
Statins are an effective treatment for the prevention of cardiovascular diseases and used extensively worldwide. However, myotoxicity induced by statins is a common adverse event and a major barrier to maximising cardiovascular risk reduction. The clinical spectrum of statin induced myotoxicity includes asymptomatic rise in creatine kinase concentration, myalgia, myositis and rhabdomyolysis. In certain cases, the cessation of statin therapy does not result in the resolution of muscular symptoms or the normalization of creatine kinase, raising the possibility of necrotizing autoimmune myopathy. There is increasing understanding and recognition of the pathophysiology and risk factors of statin induced myotoxicity. Careful history and physical examination in conjunction with selected investigations such as creatine kinase measurement, electromyography and muscle biopsy in appropriate clinical scenario help diagnose the condition. The management of statin induced myotoxicity involves statin cessation, the use of alternative lipid lowering agents or treatment regimes, and in the case of necrotizing autoimmune myopathy, immunosuppression.
In this study, we investigated the antiobesity properties of Petalonia binghamiae extract (PBE) in mice in which obesity was induced with a high-fat diet (HFD). PBE administration (150 mg/kg/day) for 70 days decreased body weight gain, adipose tissue weight, and the serum triglyceride level in mice fed a HFD. PBE reduced serum levels of glutamic pyruvic transaminase and glutamic oxaloacetic transaminase as well as the accumulation of lipid droplets in the liver. PBE restored the HFD-induced decrease in phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in epididymal adipose tissue. PBE increased the phosphorylation of AMPK and ACC and decreased the expression of SREBP1c in mature 3T3-L1 adipocytes. In addition, we further explored the active compound responsible for AMPK activation by PBE in 3T3-L1 adipocytes. Fucoxanthin isolated from PBE increased the phosphorylation of AMPK and ACC with increasing LKB1 phosphorylation in mature 3T3-L1 adipocytes. Taken together, these data suggest that PBE (or fucoxanthin) exert improving effects on HFD-induced obesity by promoting β-oxidation and reducing lipogenesis.
Differential extractions of proteins from Theobroma cacao seeds have revealed the presence of an albumin fraction and a globulin fraction with proportions of 52% and 43% respectively, of total seed proteins. In contrast to some earlier reports, we could not detect any prolamin. The 'glutelin fraction' described in the literature was found to consist of residual globulin. After fermentation, the first step in cocoa processing, the proportion of the globulin fraction is considerably reduced. The major albumin is a polypeptide with an apparent molecular weight of 19 kDa. The globulin fraction contained polypeptides with apparent molecular sizes of 47 kDa, 31 kDa, and 14.5 kDa. Globulin prepared in the absence of the aspartyl protease inhibitor pepstatin contained two additional polypeptides with apparent molecular sizes of 28 kDa and 16 kDa, respectively. The negative globulin of Theobroma cacao is a glycoprotein with a sedimentation coefficient of 7-8S and a molecular weight of 150 kDa. Its subunits are not cross-linked by disulphide bridges-in contrast to the legumin-like storage globulins which are predominant in the seeds of all other dicotyledons studied so far. Therefore, Theobroma cacao is the first plant described to date whose seeds contain a vicilin-like globulin, but apparently no legumin-class globulin.
Hydroxy-methyl-glutaryl Co-A reductase (HMGCR) inhibitors or statins are a well recognized cause of a variety of skeletal myopathic effects which generally resolve on stopping the medication. Recent reports, however, suggest that statins are associated with a unique autoimmune myopathy wherein symptoms persist or even progress after statin discontinuation and require immunosuppressive therapy. We performed a systematic review to examine the association of statins with inflammatory (dermatomyositis/polymyositis) and necrotizing myopathies.
We searched PubMed, Ovid and Scopus for English language articles addressing statin associated inflammatory and necrotizing myopathies. Given the paucity of cases, we extended the search to include articles in all languages.
The search yielded 14 articles reporting a possible association of statins with inflammatory myopathies describing 10 cases of polymyositis and 14 cases of dermatomyositis, and 4 articles reporting a possible association of statins with necrotizing myopathies describing 63 cases. One study identified a unique antibody directed against HMGCR in patients with necrotizing myopathy. Systemic immunosuppressive therapy was required in majority of these cases for resolution of symptoms.
Statins have recently been associated with a variety of inflammatory myopathies including polymyositis, dermatomyositis, and a necrotizing myopathy. The association of statins with necrotizing myopathy is strengthened by the discovery that the serum of some of these patients contains an anti-HMGCR antibody. This suggests that statins can cause or unmask an immune mediated myopathy.
Atherosclerosis is a chronic disease of the arterial wall, and a leading cause of death and loss of productive life years worldwide. Research into the disease has led to many compelling hypotheses about the pathophysiology of atherosclerotic lesion formation and of complications such as myocardial infarction and stroke. Yet, despite these advances, we still lack definitive evidence to show that processes such as lipoprotein oxidation, inflammation and immunity have a crucial involvement in human atherosclerosis. Experimental atherosclerosis in animals furnishes an important research tool, but extrapolation to humans requires care. Understanding how to combine experimental and clinical science will provide further insight into atherosclerosis and could lead to new clinical applications.
Once considered divine retribution for sins, comorbidities of obesity (metabolic syndrome) are today attributed to obesity-induced metabolic defects. Here, we propose that obesity and hyperleptinemia protect lipid-intolerant nonadipose organs against lipotoxic lipid spillover during sustained caloric surplus. Metabolic syndrome is ascribed to lipotoxicity caused by age-related resistance to antilipotoxic protection by leptin.