stilbenes and Metabolic-Syndrome

Metabolic syndrome (MS) is the term for a combination of hypertension, dyslipidemia, insulin resistance, and central obesity as factors leading to cardiovascular and metabolic disease. Epidemiological investigation has shown that polyphenol intake is negatively correlated with the incidence of MS. Natural polyphenols are widely found in cocoa beans, tea, vegetables, fruits, and some Chinese herbal medicines; they are a class of plant compounds containing a variety of phenolic structural units, which are potent antioxidants and anti-inflammatory agents in plants. Polyphenols are composed of flavonoids (such as flavanols, anthocyanidins, anthocyanins, isoflavones,

Topics: Anthocyanins; Blood Glucose; Humans; Isoflavones; Lignans; Metabolic Syndrome; Polyphenols; Stilbenes; Tea

Flavonoid resveratrol modulates the transcription factor NF-κB; inhibits the cytochrome P450 isoenzyme CYP1 A1; suppresses the expression and activity of cyclooxygenase enzymes; and modulates Fas/Fas-ligand-mediated apoptosis, p53, mammalian target of rapamycin, and cyclins and various phosphodiesterases. This increases the cytosolic cAMP that activates Epac1/CaMKKβ/AMPK/SIRT1/PGC-1α pathway, which in turn facilitates increased oxidation of fatty acids, mitochondrial biogenesis, mitochondrial respiration, and gluconeogenesis. Resveratrol triggers apoptosis of activated T cells and suppresses tumor necrosis factor-α, interluekin-17 (IL-17), and other proinflammatory molecules, and thus is of benefit in autoimmune diseases. In addition, resveratrol inhibits expression of hypoxia-inducible factor-1α and vascular endothelial growth factor, explaining its effective action against cancer. Brain-derived neurotrophic factor (BDNF) that is involved in the pathogenesis of obesity, type 2 diabetes mellitus, and metabolic syndrome is also altered in depression, schizophrenia, bipolar disorder, and autism. We noted that BDNF protects against cytotoxic actions of alloxan, streptozotocin, and benzo(a)pyrene. Resveratrol prevents bisphenol A-induced autism, type 2 diabetes mellitus, and metabolic syndrome, suggesting that it may augment BDNF synthesis and action. We also observed that BDNF levels are low in type 2 diabetes mellitus and that BDNF enhances production of antiinflammatory lipid, lipoxin A4, whose levels are low in diabetes mellitus. Thus, resveratrol may augment production of lipoxin A4. Resveratrol alters gut microbiota and influences stem cell proliferation and differentiation. These pleiotropic actions of resveratrol may explain the multitude of its actions and benefits.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Apoptosis; Autistic Disorder; Brain-Derived Neurotrophic Factor; Cell Differentiation; Cell Proliferation; Cytochrome P-450 CYP1A1; Diabetes Mellitus, Type 2; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Interleukin-17; Lipoxins; Metabolic Syndrome; NF-kappa B; Resveratrol; Stilbenes; Transcription Factors; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

Civilization development is associated with immense progress in science and significant improvement of human living conditions but simultaneously it contributes to many health problems including metabolic syndrome. Metabolic syndrome is a set of mutually associated factors including insulin resistance, hyperinsulinemia, obesity, lipids disorders and hypertension, which is the main cause of development of coronary heart disease and type 2 diabetes. The first line of defense against metabolic syndrome is a change of life style including body mass reduction, application of a low-calorie diet and performance of physical activity. In spite of the simplicity of therapy, long-term success of the above treatment among patients is observed seldom because it is very difficult to obey rigorous rules. Nowadays, it is considered that diet supplements including antioxidants, polyunsaturated fatty acids and mineral elements are helpful in metabolic syndrome treatment due to their antioxidant and anti-inflammatory properties. It is considered that a health balanced diet enriched with various diet supplements may be the best strategy in metabolic syndrome treatment.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Calcium; Caloric Restriction; Diabetes Mellitus, Type 2; Dietary Supplements; Fatty Acids, Omega-3; Garlic; Humans; Magnesium; Metabolic Syndrome; Obesity; Panax; Photinia; Phytotherapy; Plant Preparations; Resveratrol; Risk Reduction Behavior; Selenium; Stilbenes; Tea; Zinc

Obesity as part of metabolic syndrome is a major lifestyle disorder throughout the world. Current drug treatments for obesity produce small and usually unsustainable decreases in body weight with the risk of major adverse effects. Surgery has been the only treatment producing successful long-term weight loss. As a different but complementary approach, lifestyle modification including the use of functional foods could produce a reliable decrease in obesity with decreased comorbidities. Functional foods may include fruits such as berries, vegetables, fibre-enriched grains and beverages such as tea and coffee. Although health improvements continue to be reported for these functional foods in rodent studies, further evidence showing the translation of these results into humans is required. Thus, the concept that these fruits and vegetables will act as functional foods in humans to reduce obesity and thereby improve health remains intuitive and possible rather than proven.

Topics: Animals; Anthocyanins; Antioxidants; Caffeine; Dietary Fiber; Disease Models, Animal; Ellagic Acid; Fatty Acids; Feeding Behavior; Fruit; Functional Food; Humans; Metabolic Syndrome; Nutritional Physiological Phenomena; Obesity; Olive Oil; Prebiotics; Probiotics; Quercetin; Rats; Rutin; Stilbenes; Thermogenesis; Vegetables; Vitamins

Adiponectin is produced predominantly by adipocytes and plays an important role in metabolic and cardiovascular homeostasis through its insulin-sensitizing actions and anti-inflammatory and anti-atherogenic properties. Recently, it has been observed that lower levels of adiponectin can substantially increase the risk of developing type 2 diabetes, metabolic syndrome, atherosclerosis, and cardiovascular disease in patients who are obese. Circulating adiponectin levels are inversely related to the inflammatory process, oxidative stress, and metabolic dysregulation. Intensive lifestyle modifications and pharmacologic agents, including peroxisome proliferator-activated receptor-γ or α agonists, some statins, renin-angiotensin-aldosterone system blockers, some calcium channel blockers, mineralocorticoid receptor blockers, new β-blockers, and several natural compounds can increase adiponectin levels and suppress or prevent disease initiation or progression, respectively, in cardiovascular and metabolic disorders. Therefore, it is important for investigators to have a thorough understanding of the interventions that can modulate adiponectin. Such knowledge may lead to new therapeutic approaches for diseases such as type 2 diabetes, metabolic syndrome, cardiovascular disease, and obesity. This review focuses on recent updates regarding therapeutic interventions that might modulate adiponectin.

Topics: Adiponectin; Antihypertensive Agents; Atherosclerosis; Bariatric Surgery; Cardiovascular Diseases; Clinical Trials as Topic; Combined Modality Therapy; Diabetes Mellitus, Type 2; Diet, Reducing; Exercise; Humans; Hypoglycemic Agents; Insulin Resistance; Life Style; Metabolic Syndrome; Metabolism, Inborn Errors; Obesity; Peroxisome Proliferator-Activated Receptors; Receptors, Adiponectin; Resveratrol; Stilbenes

Metabolic syndrome (MS) is an obesity-associated collection of disorders, each of which contributes to cardiovascular risk. For patients with MS, it is difficult to follow a diet/exercise regime that would improve their symptoms. Therefore, the investigation of agents that may deal with its more serious aspects is an important medical field for research. Numerous experimental studies have confirmed the important role of medicinal plants or their active components in the prevention and treatment, and in lowering risk factors of MS. As oxidative stress and inflammation are involved in the association between obesity, insulin resistance (IR) and hypertension, antioxidant and anti-inflammatory plant components like polyphenols might be useful as a treatment for MS. The aqueous extract of Hibiscus Sabdariffa L (HSE), rich in several polyphenols, is commonly and effectively used in native medicines against hypertension, diabetes and liver disorders. HSE has also shown therapeutic promise in the prevention of MS in patients, probably due to its polyphenol content. Curcumins, derived from the spice turmeric, and resveratrol, polyphenols found in grapes and red wine respectively, in addition to their antioxidant and anti-inflammatory properties, inhibit preadipocyte proliferation, de novo lipogenesis and fat accumulation in liver. Thus, due to their efficacy in the regulation of multiple targets, polyphenols have received considerable interest as potential therapeutic agents for the prevention and treatment of MS. This review discusses the therapeutic use of HSE, as well as curcumin and resveratrol, in the context of obesity as an initiator of insulin resistance and hypertension, the two main features of MS, together with the underlying mechanisms of action.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Curcumin; Hibiscus; Humans; Metabolic Syndrome; Phytotherapy; Plant Extracts; Resveratrol; Stilbenes

Epidemiological studies have suggested that metabolic programming begins during fetal life and adverse events in utero are a critical factor in the etiology of chronic diseases and overall health. While the underlying molecular mechanisms linking impaired fetal development to these adult diseases are being elucidated, little is known about how we can intervene early in life to diminish the incidence and severity of these long-term diseases. This paper highlights the latest clinical and pharmaceutical studies addressing how dietary intervention in fetal and neonatal life may be able to prevent aspects of the metabolic syndrome associated with IUGR pregnancies.

Topics: Antioxidants; Ascorbic Acid; Diet Therapy; Dietary Supplements; Exenatide; Fatty Acids, Omega-3; Female; Fetal Growth Retardation; Folic Acid; Humans; Hypoglycemic Agents; Melatonin; Metabolic Syndrome; Micronutrients; Peptides; Pregnancy; Prenatal Exposure Delayed Effects; Prenatal Nutritional Physiological Phenomena; Resveratrol; Stilbenes; Venoms

Greater understanding about the pathogenesis of metabolic syndrome and potential causes suggests that plant polyphenols might be useful as a treatment. Dietary excess energy can be stored in adipocytes, leading to the release of proinflammatory cytokines and adipose-related hormones that cause vascular injury. Plant polyphenols, organic compounds found in numerous plant species and their fruits, are being actively studied as potential treatments for components of the metabolic syndrome. Individual polyphenols that have been examined include resveratrol, quercetin, epigallocathechin-3-gallate, and curcumin. Resveratrol lowers weight, blood pressure, glucose, and insulin resistance in rodents, and a human trial is currently underway. Quercetin decreases lipid and glucose levels in obese rats, and in a human investigation of subjects with the metabolic syndrome has lowered blood pressure without significant alteration of lipids. Epigallocathechin-3-gallate-induced weight loss has attenuated glucose levels and insulin resistance in rodents and improved hemoglobin A(1c) and lipid in human studies. Plant extracts also can be used. Grape seed and chokeberry extracts have decreased blood pressure and lipid levels in small human trials. Other human investigations have shown the beneficial effects of cocoa, coffee, carob, and Momordica charantia. Thus far, most studies have involved a small number of subjects and have been of short duration. Future studies should be designed to account for a disease process in which the pathogenic factors may take place for years before disease manifestations take place, the possibly limited bioavailability of polyphenols, and the potential need to provide combinations or modifications of polyphenols.

Topics: Animals; Antioxidants; Catechin; Curcumin; Flavonoids; Humans; Metabolic Syndrome; Phenols; Plant Extracts; Polyphenols; Quercetin; Resveratrol; Stilbenes

Resveratrol is a polyphenolic compound found in red wine that is believed to be responsible for its beneficial cardiovascular effects. Extensive research in the past several decades has identified multiple mechanisms by which resveratrol modifies the cardiovascular risk factors that lead to coronary artery disease, yet translation to the clinical arena has been unexpectedly slow. In this article, we review the existing evidence regarding the beneficial effects of resveratrol and briefly discuss its potential therapeutic applications.

Topics: Animals; Cardiovascular System; Coronary Artery Disease; Humans; Lipid Peroxidation; Lipids; Macrophages; Metabolic Syndrome; Muscle, Smooth, Vascular; Myocardial Reperfusion; Plaque, Atherosclerotic; Resveratrol; Stilbenes; Thrombosis; Wine

Topics: Animals; Antioxidants; Cardiovascular Diseases; Evidence-Based Medicine; Humans; Inflammation; Metabolic Syndrome; Neoplasms; Phytotherapy; Protective Agents; Resveratrol; Stilbenes

The metabolic syndrome is associated with increased risk for development of both cardiovascular disease and type 2 diabetes in humans. Because experimental data and clinical experience have shown that metabolic syndrome and caloric restriction have, at least partly, opposite pathophysiological pathways, the activation of sirtuins may constitute a pharmacological approach to treat metabolic syndrome. Resveratrol is a polyphenol produced by plants that has multiple beneficial activities similar to those associated with caloric restriction.. Through its regulatory action of both AMP kinase and the sirtuin sirtuin-1, resveratrol is a natural sirtuin activator that certainly will be the head of a new pharmacological family of drugs targeted on sirtuin-1 activity exacerbation in order to treat/protect from obesity and diabetes, and thus metabolic syndrome.. This review discusses the therapeutic use of resveratrol and sirtuin activators in the context of insulin resistance and obesity, the two main features of metabolic syndrome.

Topics: Adenylate Kinase; Caloric Restriction; Humans; Metabolic Syndrome; Phytotherapy; Plant Extracts; Resveratrol; Sirtuin 1; Stilbenes

Following on from impressive economic development and urbanization, China is currently experiencing a high prevalence of metabolic syndrome. Patients with metabolic syndrome suffer from the "The Deadly Quartet" of hyperglycemia, hypertriglyceridemia, hypertension, and central (or upper body) obesity. Current treatment strategies directed towards metabolic syndrome tend to be limited to just one of these four conditions, so developing novel drugs to target multiple metabolic abnormalities could be preferable to current approaches. New insights suggest benefits of natural agents as treatments for metabolic syndrome. Herein, we review the evidence for using nine such agents developed on the basis of traditional medicine or herbal preparations.

Topics: Animals; Anthocyanins; Berberine; China; Curcumin; Female; Flavanones; Genistein; Ginsenosides; Humans; Male; Medicine, Traditional; Metabolic Syndrome; Mice; Momordica charantia; Phytotherapy; Plant Preparations; Prevalence; Randomized Controlled Trials as Topic; Rats; Resveratrol; Stilbenes

Several experimental studies and some clinical experience have shown that metabolic syndrome and caloric restriction exert opposite effects on thrombosis, because these two nourishing conditions are at extreme ends of the same spectrum. The antithrombotic action induced by caloric restriction happens through Sirtuin 1 (SIRT1), a gene/protein activated by the reduction of calorie intake lower than is typical. The antithrombotic effect is due to the activation of SIRT1 acting through an increase of insulin sensitivity, which reduces endothelial dysfunction. Sirtuins have been implicated in several processes, including genomic stability, DNA repair, apoptosis, and adipogenesis. In addition, they have been shown to promote longevity in simple eukaryotes. Some compounds, such as resveratrol, mimic the action of SIRT1 and seem able to correct the prothrombotic state induced by metabolic syndrome. To confirm this, we demonstrated that resveratrol improved the left ventricular function of type 2 diabetics who suffered recent acute myocardial infarction (AMI) when a moderate red wine amount (containing resveratrol) was taken daily by patients receiving conventional antiischemic therapy, in comparison with another group treated with antiischemic compounds alone.

Topics: Animals; Blood Coagulation; Caloric Restriction; Fibrinolytic Agents; Humans; Metabolic Syndrome; Myocardial Ischemia; Resveratrol; Sirtuins; Stilbenes; Thrombosis; Ventricular Function, Left; Wine

Resveratrol (3,4',5 trihydroxystilbene), a naturally-occurring molecule known as a phytoalexin, is synthesized by plants in response to attacks by fungi, bacteria, or other injurious substances; it is also known to possess an array of cardioprotective effects. Recently, studies have shown resveratrol to protect against the metabolic changes associated with hypercaloric diets in mice with induced insulin resistance, hyperglycemia, and dyslipidemia. Despite impressive gains in diagnosis and treatment, cardiovascular disease (CVD) remains a serious clinical problem and threat to public health. The metabolic syndrome, which identifies persons at higher risk for diabetes mellitus and CVD, is approaching a prevalence of nearly 25% of the western world. If the metabolic syndrome can be considered a polar opposite to caloric restriction, then agents that mimic caloric restriction may offer a new therapeutic approach to preventing CVD. The authors discuss the cardioprotective effects of resveratrol and highlight its role in glucose homeostasis and lipid metabolism in mice. Armed with the ability to prevent the deleterious effects of excess caloric intake and prevent detrimental cardiovascular events, resveratrol merits proper clinical investigations for its efficacy in treating metabolic diseases and CVD.

Topics: Animals; Blood Glucose; Caloric Restriction; Cardiovascular Agents; Cardiovascular Diseases; Dietary Carbohydrates; Dietary Fats; Energy Intake; Homeostasis; Humans; Lipid Metabolism; Metabolic Syndrome; Molecular Structure; Resveratrol; Sirtuin 1; Sirtuins; Stilbenes

The metabolic syndrome (MetS) encompasses a constellation of cardio-metabolic abnormalities associated with a high risk of developing type 2 diabetes and cardiovascular disease (CVD), the top killer in the ageing population. Recent studies have demonstrated multiple beneficial effects of moderate wine consumption in the protection against development of the MetS and its related medical complications. The association of moderate wine consumption with lower incidence of the MetS and atherosclerotic heart disease has been repeatedly documented in numerous epidemiological studies on diverse ethnic groups. In addition to the favorable effects of moderate ethanol intake on lipid profiles, polyphenols enriched in red wine possess multiple benefits on the MetS beyond alcohol through their anti-oxidant, anti-inflammatory, vascular-protective and insulin-sensitizing properties. Notable among these red wine polypheolic compounds is resveratrol, a phytoalexin that has recently attracted great attention due to its role in mimicking calorie restriction. This compound can act as a potent activator of the NAD(+)-dependent deacetylases sirtuins to expand the life span and to prevent the deleterious effects of excess intake on insulin resistance and metabolic derangement. In addition, resveratrol exerts its multiple protective effects against the MetS through stimulating AMP-activated protein kinase and promoting mitochondria biogenesis. In this review, we highlight the recent epidemiological and experimental evidences supporting the protective effects of moderate wine intake against the MetS and its associated cardio-metabolic complications, and discuss the molecular mechanisms underlying the multiple beneficial actions of red wine polyphenols with the focus on resveratrol.

Topics: Alcohol Drinking; Animals; Antioxidants; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Insulin Resistance; Metabolic Syndrome; Randomized Controlled Trials as Topic; Resveratrol; Stilbenes; Wine

Calorie restriction (CR) extends lifespan in a wide variety of species and mitigates diseases of aging in mammals. Here, we describe the evidence that the silent information regulator 2 (SIR2) gene, which encodes a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase, regulates lifespan and mediates CR in lower species such as Saccharomyces cerevisiae and Caenorhabditis elegans. We discuss the emerging roles of mammalian SIR2 homologs in regulating physiological changes triggered by CR and their potential connections to diseases of aging. We conclude with the recent advances on small molecules that activate the enzymatic activity of SIR2 as potential CR mimetics. The SIR2 family represents an evolutionarily conserved lifespan regulator. Modulating the activity of SIR2 might provide effective CR mimetics to combat diseases of aging.

Topics: Aging; Animals; Caenorhabditis elegans; Caloric Restriction; Enzyme Inhibitors; Humans; Longevity; Metabolic Syndrome; Models, Biological; Nerve Degeneration; Resveratrol; Saccharomyces cerevisiae; Sirtuins; Stilbenes

Low-grade inflammation is associated with obesity and the metabolic syndrome (MetS). Preclinical evidence suggests that resveratrol (RSV) has beneficial metabolic and anti-inflammatory effects that could have therapeutic implications.. To investigate effects of long-term RSV treatment on inflammation and MetS.. A randomized, placebo-controlled, double-blind, parallel group clinical trial conducted at Aarhus University Hospital.. Middle-aged community-dwelling men (N = 74) with MetS, 66 of whom completed all visits (mean ± standard error of the mean): age, 49.5 ± 0.796 years; body mass index, 33.8 ± 0.44 kg/m2; waist circumference, 115 ± 1.14 cm.. Daily oral supplementation with 1000 mg RSV (RSVhigh), 150 mg RSV, or placebo for 16 weeks.. Plasma levels of high-sensitivity C-reactive protein (hs-CRP), circulating lipids, and inflammatory markers in circulation and adipose/muscle tissue biopsy specimens; glucose metabolism; and body composition including visceral fat and ectopic fat deposition.. RSV treatment did not lower circulating levels of hs-CRP, interleukin 6, or soluble urokinase plasminogen activator receptor in plasma, and inflammatory gene expression in adipose and muscle tissues also remained unchanged. RSV treatment had no effect on blood pressure, body composition, and lipid deposition in the liver or striated muscle. RSV treatment had no beneficial effect on glucose or lipid metabolism. RSVhigh treatment significantly increased total cholesterol (P < 0.002), low-density lipoprotein (LDL) cholesterol (P < 0.006), and fructosamine (P < 0.013) levels compared with placebo.. RSV treatment did not improve inflammatory status, glucose homeostasis, blood pressure, or hepatic lipid content in middle-aged men with MetS. On the contrary, RSVhigh significantly increased total cholesterol, LDL cholesterol, and fructosamine levels compared with placebo.

Topics: Absorptiometry, Photon; Adipose Tissue; Antioxidants; Blood Glucose; Blood Pressure; Blotting, Western; Body Composition; C-Reactive Protein; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Double-Blind Method; Fructosamine; Humans; Insulin; Insulin Resistance; Interleukin-6; Intra-Abdominal Fat; Leptin; Liver; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Metabolic Syndrome; Middle Aged; Muscle, Skeletal; Quadriceps Muscle; Real-Time Polymerase Chain Reaction; Receptors, Urokinase Plasminogen Activator; Resveratrol; Stilbenes; Triglycerides

Isolated phytochemicals have been shown to reduce blood pressure; however, combinations of phytochemicals have rarely been tested in humans. We hypothesized that a combination of extracts from grape seed and skin (330 mg), green tea (100 mg), resveratrol (60 mg) and a blend of quercetin, ginkgo biloba and bilberry (60 mg) would reduce blood pressure (BP) in hypertensive subjects.. Eighteen individuals meeting BP requirements (⩾130 mm Hg systolic or ⩾85 mm Hg diastolic) and criteria for metabolic syndrome were enrolled in a double-blinded, placebo-controlled, crossover trial (ClinicalTrials.gov, NCT01106170). The 28-day placebo and supplement arms were separated by a 2-week washout period, and 14 -h daytime ambulatory BP was assessed at baseline and at the end point of each arm.. BP was not altered after placebo. After supplement treatment, diastolic pressure was reduced by 4.4 mm Hg (P=0.024, 95% CI, 0.6-8.1), systolic pressure was unchanged and mean arterial pressure trended (P=0.052) toward reduction. Serum angiotensin-converting enzyme activity was similar between placebo and supplement arms, but urinary nitrate and nitrite concentrations were significantly increased (P=0.022) after supplementation. Human aortic endothelial cells treated with metabolites of the polyphenols used in the human supplement trial had a significant increase (P=0.005) in insulin-stimulated eNOS phosphorylation and greater (P<0.001) accumulation of nitrates/nitrites.. Our clinical and in vitro data support the theory that this combination of polyphenols reduced diastolic pressure by potentiating eNOS activation and nitric oxide production. Such supplements may have clinical relevance as stand-alone or adjunct therapy to help reduce BP.

Topics: Adult; Antihypertensive Agents; Antioxidants; Blood Pressure; Cross-Over Studies; Dietary Supplements; Double-Blind Method; Endothelium, Vascular; Female; Humans; Hypertension; Magnoliopsida; Male; Metabolic Syndrome; Middle Aged; Nitric Oxide; Nitric Oxide Synthase Type III; Phytochemicals; Phytotherapy; Plant Extracts; Polyphenols; Quercetin; Resveratrol; Stilbenes

Resveratrol is a naturally occurring polyphenol with purported inhibitory effects on prostate growth and cancer development. A number of studies have demonstrated that resveratrol reduces prostate growth in animal models and reduces prostate cell growth in vitro. Based on these pre-clinical findings, interest in resveratrol is increasing in relation to the management of benign prostate hyperplasia (BPH) and prostate cancer. So far, no human trials have evaluated the effects of resveratrol on circulating androgens, prostate size, or biochemical markers of prostate size.. In a randomized placebo controlled clinical study using two doses of resveratrol (150 mg or 1,000 mg resveratrol daily) for 4 months, we evaluated the effects on prostate size, prostate specific antigen (PSA) and sex steroid hormones in 66 middle-aged men suffering from the metabolic syndrome(MetS).. At baseline, prostate size and PSA were positively correlated (R = 0.34, P < 0.007) as was prostate size and age (R = 0.37, P < 0.003). Prostate size did not correlate with testosterone, free testosterone, dihydrotestosterone (DHT), or any other androgen precursor at baseline. The highest dose of resveratrol lowered the serum level of androstenedione 24% (P = 0.052), dehydroepiandrosterone (DHEA) 41% (P < 0.01), and dehydroepiandrosterone-sulphate (DHEAS) 50% (p<0.001), compared to the control group. However, prostate size and levels of PSA, testosterone, free testosterone and DHT remained unchanged.. In this population of middle-aged men suffering from MetS, high dose resveratrol (1,000 mg daily) administration for 4 months significantly lowered serum levels of the androgen precursors androstenedione, DHEA and DHEAS, whereas prostate size and circulating levels of PSA, testosterone, free testosterone, and dihydrotestosterone were unaffected. The present study suggests that resveratrol does not affect prostate volume in healthy middle-aged men as measured by PSA levels and CT acquired prostate volumes. Consequently, we find no support for the use of resveratrol in the treatment of benign prostate hyperplasia.

Topics: Aged; Androgens; Antineoplastic Agents, Phytogenic; Biomarkers, Tumor; Dihydrotestosterone; Double-Blind Method; Humans; Male; Metabolic Syndrome; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Regression Analysis; Resveratrol; Stilbenes; Testosterone; Testosterone Congeners

This study evaluated the effect of resveratrol administration on metabolic syndrome, insulin sensitivity, and insulin secretion.. A randomized, double-blind, placebo-controlled clinical trial was carried out in 24 patients with diagnosis of metabolic syndrome in accordance with the International Diabetes Federation criteria. Glucose and insulin levels were measured after a 75-gram dextrose load. Triglycerides and high-density lipoprotein cholesterol concentrations at baseline were also evaluated. Twelve patients received trans-resveratrol (500 mg) three times per day before meals for 90 days. The remaining 12 patients received placebo at the same dose. The area under the curve (AUC) values of glucose and insulin, total insulin secretion, first-phase of insulin secretion, and insulin sensitivity were calculated.. After resveratrol administration, there were significant differences in total weight (94.4±13.2 vs. 90.5±12.3 kg, P=0.007), body mass index (BMI) (35.6±3.2 vs. 34.3±3.0 kg/m(2), P=0.006), fat mass (41.2±7.9 vs. 38.8±6.0 kg, P=0.001), and waist circumference (WC) (109±9 vs. 105±10 cm, P=0.004). There were also significant differences in AUC of insulin (48,418±22,707 vs. 26,473±8,273 pmol/L, P=0.003) and insulinogenic index (0.48±0.22 vs. 0.28±0.08, P=0.004).. Administration of resveratrol significantly decreases weight, BMI, fat mass, WC, AUC of insulin, and total insulin secretion.

Topics: Adiposity; Adult; Area Under Curve; Biomarkers; Blood Glucose; Body Mass Index; Cholesterol, HDL; Double-Blind Method; Female; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Male; Metabolic Syndrome; Mexico; Middle Aged; Predictive Value of Tests; Resveratrol; Stilbenes; Time Factors; Treatment Outcome; Triglycerides; Weight Loss

Metabolic syndrome (MetS) is associated with low-grade inflammation, which may harmfully affect bone. Resveratrol (RSV) possesses anti-inflammatory properties, and rodent studies suggest bone protective effects.. This study sought to evaluate effects of RSV treatment on bone in men with MetS.. The study was conducted at Aarhus University Hospital as a randomized, double-blinded, placebo-controlled trial assessing changes in bone turnover markers, bone mineral density (BMD), and geometry.. The study population comprised 74 middle-aged obese men with MetS recruited from the general community, of which 66 completed all visits. Mean age of participants was 49.3 ± 6.3 years and mean body mass index was 33.7 ± 3.6 kg/m(2).. Oral treatment with 1.000 mg RSV (RSV(high)), 150 mg RSV (RSV(low)), or placebo daily for 16 weeks.. Prespecified primary endpoint was change in bone alkaline phosphatase (BAP).. BAP increased dose dependently with RSV (R = 0.471, P < .001), resulting in a significantly greater increase in BAP in the RSV(high) group compared with placebo at all time-points (week 4, 16.4 ± 4.2%, P < .001; week 8, 16.5 ± 4.1%, P < .001; week 16, 15.2 ± 3.7%, P < .001). Lumbar spine trabecular volumetric bone mineral density (LS vBMD(trab)) also increased dose dependently with RSV (R = 0.268, P = .036), with a significant increase of 2.6 ± 1.3% in the RSV(high) group compared with placebo (P = .043). In addition, changes in BAP and LS vBMD(trab) were positively correlated (R = 0.281, P = .027). No consistent changes were detected in bone density at the hip.. Our data suggest that high-dose RSV supplementation positively affects bone, primarily by stimulating formation or mineralization. Future studies of longer duration comprising populations at risk of osteoporosis are needed to confirm these results.

Topics: Absorptiometry, Photon; Alkaline Phosphatase; Antioxidants; Bone and Bones; Bone Density; Double-Blind Method; Humans; Male; Metabolic Syndrome; Middle Aged; Obesity; Patient Compliance; Resveratrol; Stilbenes

Psoriasis is a systemic inflammatory immune-mediated skin disease. Recently a relationship with metabolic syndrome in terms of psoriasis severity and response to therapy was observed.. We performed an open-label randomized controlled study to evaluate the role of a nutraceutical containing Q10 coenzyme, Krill-oil, lipoic acid, resveratrol, Vitis vinifera seed oil, vitamin E and selenium in addition to etanercept therapy for patients affected by psoriasis and metabolic syndrome. Forty patients were enrolled and divided into two arms, one receiving only etanercept, one other receiving also the neutraceutical. After a period of 3 months (T1) a second evaluation of the considered parameters was performed.. At T1 statistically significant differences were detected in HDL cholesterol and triglycerides values both comparing the two arms and in the nutraceutical arm.. Our results show that the dietary addiction of the nutraceutical to the etanercept therapy in patients affected by both psoriasis and metabolic syndrome could help to restore the normal lipid profile.

Topics: Adult; Animals; Antioxidants; Biomarkers; Body Mass Index; Cholesterol, HDL; Dietary Fats, Unsaturated; Dietary Supplements; Etanercept; Euphausiacea; Female; Follow-Up Studies; Humans; Immunoglobulin G; Immunosuppressive Agents; Male; Metabolic Syndrome; Middle Aged; Psoriasis; Receptors, Tumor Necrosis Factor; Resveratrol; Seeds; Selenium; Severity of Illness Index; Stilbenes; Thioctic Acid; Treatment Outcome; Triglycerides; Tumor Necrosis Factor-alpha; Ubiquinone; Vitamin E; Vitis

Resveratrol is known to improve endothelial function in animals, but little is known about its effect on human subjects. Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors underlying endothelial dysfunction. We hypothesized that the modified resveratrol, Longevinex, improves endothelial function in patients with MetS. Thirty-four patients who had been treated for MetS and lifestyle-related disease were randomly assigned to group A, in which Longevinex was administered for 3 months and then discontinued for 3 months, whereas in the time-matched group B, Longevinex was administered between 3 and 6 months. These 2 groups of patients received similar drugs at baseline for diabetes mellitus, dyslipidemia, or hypertension. Flow-mediated dilatation significantly increased during the administration of Longevinex but decreased to baseline 3 months after the discontinuation of Longevinex in the group A patients. Conversely, in the group B patients, flow-mediated dilatation remained unchanged for the first 3 months without Longevinex but was significantly increased 3 months after the treatment with Longevinex. Longevinex did not significantly affect blood pressure, insulin resistance, the lipid profile or inflammatory markers during 6-month follow-up. These results demonstrate that Longevinex specifically improves endothelial function in subjects with MetS who were receiving standard therapy for lifestyle-related disease.

Topics: Aged; Diabetes Mellitus; Drug Compounding; Endothelium, Vascular; Female; Humans; Hyperlipidemias; Hypertension; Insulin Resistance; Life Style; Male; Metabolic Syndrome; Middle Aged; Resveratrol; Stilbenes; Vasodilation; Vasodilator Agents

Metabolic syndrome (MetS) is associated with dementia, but it is unclear whether MetS is related to Alzheimer's disease (AD). We investigated the association of MetS with brain amyloid, a key AD feature, and neurodegeneration. A community-based sample of 350 middle-aged Hispanics in New York City had cerebral amyloid β (Aβ) burden ascertained with

Topics: Age Factors; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Blood Glucose; Brain; Diffusion Tensor Imaging; Female; Hispanic or Latino; Humans; Male; Metabolic Syndrome; Middle Aged; Nerve Degeneration; New York; Risk; Stilbenes; Triglycerides

Topics: Acetyl-CoA Carboxylase; Animals; Benzoxazoles; Body Weight; Diabetes Mellitus; Enzyme Activators; Fatty Acid Synthases; Fatty Liver; Gene Expression Regulation; Glucose Intolerance; Heterocyclic Compounds, 4 or More Rings; Hypoglycemic Agents; Male; Metabolic Syndrome; Mice, Inbred C57BL; Molecular Docking Simulation; Resveratrol; Sirtuin 1; Sterol Regulatory Element Binding Proteins; Stilbenes

The purpose of this study was to evaluate probable protective effects of resveratrol treatment on hepatic oxidative events in a rat model of metabolic syndrome (MetS).. Thirty-two male adult rats were randomly divided into 4 groups: control, fructose, resveratrol, and fructose plus resveratrol. To induce MetS, fructose solution (20 % in drinking water) was used. Resveratrol (10 mg/kg/day) was given by oral gavage. All treatments were given for 8 weeks. Serum lipid profile, glucose and insulin levels, liver total oxidant status (TOS) levels and paraoxonase (PON), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities were analyzed.. Fructose-fed rats displayed statistically significant increases in TOS levels, and decreases in PON activity compared to the control group. Resveratrol treatment moderately prevented the decrease in liver PON activity caused by fructose. On the other hand, resveratrol, alone or in combination with fructose, did not change the TOS levels when compared to the fructose group. The SOD and CAT activities in all groups did not change.. In this experimental design, high-fructose consumption led to elevated TOS levels and low PON activities. The resveratrol therapy shown beneficial effects on PON activity. However, it was found to behave like a prooxidant when administered together with fructose and alone in some parameters. Our results can inspire the development of new clinical therapy in patients with MetS (Tab. 2, Ref. 34).

Topics: Animals; Antioxidants; Fructose; Glutathione Peroxidase; Insulin Resistance; Liver; Male; Metabolic Syndrome; Oxidants; Oxidative Stress; Rats; Resveratrol; Stilbenes; Superoxide Dismutase

This paper researches on the protective effects of antioxidants on metabolic syndrome induced by thyroid dysfunction. While the role of Lipoic acid (LA), Resveratrol (R) and Quercetin (Q) are recognized, the mechanisms for their ameliorative effects are partially understood. Therefore, the objective of this study was to determine the prevalence of MS among university workers and to examine the relationship with thyroid function and mechanisms for protective effects of LA, Resveratrol and Quercetin on the heart, kidneys and lungs.. In the cross-sectional study, a total of 2273 university workers (1198 males and 1075 females) aged 22-60 participated. Anthropometric measurements (weight and height), blood pressure, fasting plasma glucose (FPG), lipids, liver and kidney function tests were carried out, thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), total antioxidant capacity (T-AOC), lipid peroxidation products, malondialdehyde (MDA), advanced oxidation protein products (AOPP) and dityrosine levels were measured.. A further evaluation of oxidative stress markers in subclinical hypothyroidism (SCH) compared with normal thyroid function showed the differences. Among middle-aged men with SCH (n = 467), MDA concentrations (8.11 ± 1.39 nmol/ml) were significantly higher euthyroid controls (7.34 ± 1.31 nmol/ml; n = 190) while AOPP, dityrosine and T-AOC levels were not different.. It was demonstrated that prevalence of MS components was high. Targeting thyroid hormone restoration, inhibition of ACE and GSK3β via PI3K/AKT signaling pathway using LA, Resveratrol and Quercetin are potential novel therapeutic approaches for developing pharmaceuticals that could make significance in MS treatment.

Topics: Adult; Anthropometry; Antioxidants; Biomarkers; Cross-Sectional Studies; Female; Humans; Hypothyroidism; Male; Metabolic Syndrome; Middle Aged; Oxidative Stress; Quercetin; Resveratrol; Stilbenes; Thioctic Acid; Thyroid Function Tests; Thyroid Hormones; Thyrotropin

The present investigation was designed to explore the effectiveness of pterostilbene (PT) on insulin resistance, metabolic syndrome and oxidative stress in fructose-fed insulin resistant rats.. Age-matched, male Sprague-Dawley rats (330±30g body weight) were allocated into five groups (n=10). Control (C) group received 65% cornstarch, and the diabetic (D) group received 65% fructose for eight weeks. The third group (D+PT20) received 65% fructose and PT 20mg/kg/day for eight weeks. The fourth group (D+PT40) received 65% fructose and PT 40mg/kg/day for eight weeks. The fifth group (D+M) received 65% fructose and metformin (M) 100mg/kg/day for eight weeks. PT was dissolved in 10% β-cyclodextrin and given orally to rats. Several biochemical parameters were determined to assess the PT efficacy against insulin resistance, metabolic complications, and hepatic oxidative stress.. Significantly high HOMA-IR (p<0.001) values in D group compared to C group indicate the presence of insulin resistance. Significantly high levels of TBARS (p<0.001) and decreased levels of SOD (p<0.001) and GSH (p<0.001) in hepatic tissues of D group indicate oxidative stress associated with insulin resistance. Pterostilbene treatment to fructose-fed diabetic rats significantly decreased HOMA-IR (p<0.001) values. Furthermore, PT treatment significantly decreased hepatic TBARS (p<0.001) and increased SOD (p<0.001) and GSH (p<0.001) levels in fructose-fed diabetic rats.. Current study reveals that PT is successful in ameliorating glycemic control, insulin sensitivity while diminishing metabolic disturbances and hepatic oxidative stress in a fructose-induced T2DM rat model.

Topics: Animals; beta-Cyclodextrins; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Fructose; Insulin Resistance; Male; Metabolic Syndrome; Metformin; Oxidative Stress; Rats; Rats, Sprague-Dawley; Stilbenes; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances

Resveratrol possesses several beneficial metabolic effects in rodents, while the effects of resveratrol in humans remain unclear. Therefore, we performed a non-targeted comprehensive metabolomic analysis on blood, urine, adipose tissue, and skeletal muscle tissue in middle-aged men with metabolic syndrome randomized to either resveratrol or placebo treatment for four months. Changes in steroid hormones across all four matrices were the most pronounced changes observed. Resveratrol treatment reduced sulfated androgen precursors in blood, adipose tissue, and muscle tissue, and increased these metabolites in urine. Furthermore, markers of muscle turnover were increased and lipid metabolism was affected, with increased intracellular glycerol and accumulation of long-chain saturated, monounsaturated, and polyunsaturated (n3 and n6) free fatty acids in resveratrol-treated men. Finally, urinary derivatives of aromatic amino acids, which mainly reflect the composition of the gut microbiota, were altered upon resveratrol treatment. In conclusion, the non-targeted metabolomics approach applied to four different matrices provided evidence of subtle but robust effects on several metabolic pathways following resveratrol treatment for four months in men with metabolic syndrome-effects that, for the most part, would not have been detected by routine analyses. The affected pathways should be the focus of future clinical trials on resveratrol's effects, and perhaps particularly the areas of steroid metabolism and the gut microbiome.

Topics: Adipose Tissue; Biomarkers; Blood Pressure; Gastrointestinal Microbiome; Humans; Insulin Resistance; Male; Metabolic Syndrome; Metabolomics; Middle Aged; Muscles; Obesity; Randomized Controlled Trials as Topic; Resveratrol; Stilbenes

Uncoupling proteins (UCPs) are members of the mitochondrial anion carrier superfamily involved in the control of body temperature and energy balance regulation. They are currently proposed as therapeutic targets for treating obesity and metabolic syndrome (MetS). We studied the gene expression regulation of UCP1, -2, and -3 in abdominal white adipose tissue (WAT) from control and MetS rats treated with two doses of a commercial mixture of resveratrol (RSV) and quercetin (QRC). We found that UCP2 was the predominantly expressed isoform, UCP3 was present at very low levels, and UCP1 was undetectable. The treatment with RSV + QRC did not modify UCP3 levels; however, it significantly increased UCP2 mRNA in control and MetS rats in association with an increase in oleic and linoleic fatty acids. WAT from MetS rats showed a significantly increased expression of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ when compared to the control group. Furthermore, PPAR-α protein levels were increased by the highest dose of RSV + QRC in the control and MetS groups. PPAR-γ expression was only increased in the control group. We conclude that the RSV + QRC treatment leads to overexpression of UCP2, which is associated with an increase in MUFA and PUFA, which might increase PPAR-α expression.

Topics: Adipose Tissue, White; Animals; Gene Expression Regulation; Insulin; Linoleic Acid; Male; Metabolic Syndrome; Mitochondrial Uncoupling Proteins; Oleic Acid; Peroxisome Proliferator-Activated Receptors; Quercetin; Radioimmunoassay; Rats; Rats, Wistar; Resveratrol; RNA, Messenger; Stilbenes; Uncoupling Protein 1; Uncoupling Protein 2; Uncoupling Protein 3

Arterial stiffness, a major cardiovascular risk factor, develops within 2 months in mice fed a high-fat, high-sucrose (HFHS) diet, serving as a model of human metabolic syndrome, and it is associated with activation of proinflammatory and oxidant pathways in vascular smooth muscle (VSM) cells. Sirtuin-1 (SirT1) is an NAD(+)-dependent deacetylase regulated by the cellular metabolic status. Our goal was to study the effects of VSM SirT1 on arterial stiffness in the context of diet-induced metabolic syndrome. Overnight fasting acutely decreased arterial stiffness, measured in vivo by pulse wave velocity, in mice fed HFHS for 2 or 8 months, but not in mice lacking SirT1 in VSM (SMKO). Similarly, VSM-specific genetic SirT1 overexpression (SMTG) prevented pulse wave velocity increases induced by HFHS feeding, during 8 months. Administration of resveratrol or S17834, 2 polyphenolic compounds known to activate SirT1, prevented HFHS-induced arterial stiffness and were mimicked by global SirT1 overexpression (SirT1 bacterial artificial chromosome overexpressor), without evident metabolic improvements. In addition, HFHS-induced pulse wave velocity increases were reversed by 1-week treatment with a specific, small molecule SirT1 activator (SRT1720). These beneficial effects of pharmacological or genetic SirT1 activation, against HFHS-induced arterial stiffness, were associated with a decrease in nuclear factor kappa light chain enhancer of activated B cells (NFκB) activation and vascular cell adhesion molecule (VCAM-1) and p47phox protein expressions, in aorta and VSM cells. In conclusion, VSM SirT1 activation decreases arterial stiffness in the setting of obesity by stimulating anti-inflammatory and antioxidant pathways in the aorta. SirT1 activators may represent a novel therapeutic approach to prevent arterial stiffness and associated cardiovascular complications in overweight/obese individuals with metabolic syndrome.

Topics: Animals; Blotting, Western; Cardiovascular Diseases; Diet, High-Fat; Disease Models, Animal; Glucose Tolerance Test; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Muscle, Smooth, Vascular; Obesity; Pulse Wave Analysis; Random Allocation; Real-Time Polymerase Chain Reaction; Resveratrol; Sirtuin 1; Stilbenes; Vascular Cell Adhesion Molecule-1; Vascular Stiffness

Resveratrol has been shown to improve cardiac perfusion and ventricular function after chronic ischemic injury. Using proteomic analysis, we sought to objectively investigate potential mechanisms, by which resveratrol exerts its cardioprotective effects in the setting of metabolic syndrome and chronic myocardial ischemia. Yorkshire swine were divided into two groups based on diet: high cholesterol (n=7) or a high-cholesterol diet with supplemental resveratrol (n=6). Four weeks later, all animals underwent surgical placement of an ameroid constrictor to their left circumflex artery. Diets were continued for another 7 weeks, and then the ischemic myocardium was harvested for proteomics analysis. Proteomic analysis identified 669 common proteins between the two groups. Of these proteins, 76 were statistically different, of which 41 were characterized (P<.05). Pathway analysis demonstrated that in animals supplemented with resveratrol, there was a downregulation in several proteins involved with mitochondrial dysfunction, cell death, and unfavorable cardiac remodeling. Furthermore, there was an upregulation in proteins involved in free radical elimination. We conclude that resveratrol supplementation significantly alters several critical protein markers in the chronically ischemic myocardium. Further investigation of these proteins may help elucidate the mechanisms by which resveratrol exerts its cardioprotective effects.

Topics: Animals; Antioxidants; Biomarkers; Cell Death; Cholesterol, Dietary; Coronary Vessels; Dietary Supplements; Disease Models, Animal; Heart; Male; Metabolic Syndrome; Mitochondria; Myocardial Ischemia; Myocardium; Phytotherapy; Plant Extracts; Proteins; Proteomics; Resveratrol; Signal Transduction; Stilbenes; Swine

A defect in neo-vascularization process involving circulating angiogenic mononuclear cells (CACs) dysfunction is associated with diabetes. We showed that oxidative stress was elevated in CACs cultured from blood of individuals with metabolic syndrome (MetS) and diabetes. We then assessed the action of palmitic acid (PA), a deregulated and increased NEFA in metabolic disorders, focusing on its oxidant potential. We observed that the phyto-polyphenol resveratrol normalized oxidative stress both in CACs isolated from MetS patients or treated with PA. Resveratrol further decreased the deleterious action of PA on gene expression of vascularization factors (TNFα, VEGF-A, SDF1α, PECAM-1, VEGFR2, Tie2 and CXCR4) and improved CAC motility. Particularly, resveratrol abolished the PA-induced over-expression of the pro-oxidant protein p66Shc. Neither KLF2 nor SIRT1, previously shown in resveratrol and p66Shc action, was directly involved. Silencing p66Shc normalized PA action on VEGF-A and TNFα specifically, without abolishing the PA-induced oxidative stress, which suggests a deleterious role of p66Shc independently of any major modulation of the cellular oxidative status in a high NEFA levels context. Besides showing that resveratrol reverses PA-induced harmful effects on human CAC function, certainly through profound cellular modifications, we establish p66Shc as a major therapeutic target in metabolic disorders, independent from glycemic control.

Topics: Antioxidants; Case-Control Studies; Cell Movement; Cells, Cultured; Diabetes Mellitus, Type 2; Gene Expression Regulation; Gene Silencing; Humans; Leukocytes, Mononuclear; Male; Metabolic Syndrome; Middle Aged; Neovascularization, Physiologic; Oxidative Stress; Palmitic Acid; Resveratrol; Shc Signaling Adaptor Proteins; Src Homology 2 Domain-Containing, Transforming Protein 1; Stilbenes

Chronic inflammation and hyperglycaemia, typical features of metabolic diseases, trigger endothelial damage and release of E-selectin, a marker of endothelial activation. In the present study, we investigated molecular pathways involved in the regulation of endothelial cell activation induced by tumour necrosis factor-α (TNF-α) and high glucose. In cultured human umbilical vein endothelial cells (HUVECs), we studied the role of HuR, an ELAV (embryonic lethal, abnormal vision, Drosophila) family RNA-binding protein, and Sirtuin 1 (SIRT1) on E-selectin release and cell adhesion at different glucose concentrations. HuR expression and binding to SIRT1 were also analysed ex vivo in peripheral blood mononuclear cells (PBMCs) of subjects with and without the metabolic syndrome (MS), by immunoprecipitation (IP) of the ribonucleoprotein (RNP) complex. We found that SIRT1 overexpression prevented TNF-α- and high-glucose-dependent nuclear factor-κB (NF-κB)-p65 acetylation, E-selectin promoter activity, E-selectin release and adhesion of THP-1 cells to HUVECs. The same was mimicked by HuR overexpression, which binds and stabilizes SIRT1 mRNA. Importantly, in PBMCs of individuals with MS compared with those without, SIRT1 expression was lower, and the ability of HuR to bind SIRT1 mRNA was significantly reduced, while plasma E-selectin was increased. We conclude that post-transcriptional stabilization of SIRT1 by HuR represses inflammation- and hyperglycaemia-induced E-selectin release and endothelial cell activation. Therefore, increasing SIRT1 expression represents a strategy to counter the accelerated vascular disease in metabolic disorders.

Topics: Acetylation; Adhesiveness; Benzamides; Cell Adhesion; E-Selectin; ELAV Proteins; Endothelial Cells; Gene Expression Regulation; Glucose; Human Umbilical Vein Endothelial Cells; Humans; Hyperglycemia; Leukocytes, Mononuclear; Metabolic Syndrome; Naphthols; NF-kappa B; Protein Stability; Resveratrol; Sirtuin 1; Stilbenes; Tumor Necrosis Factor-alpha

Topics: Female; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Male; Metabolic Syndrome; Stilbenes

Resveratrol has been clinically shown to possess a number of human health benefits. As a result, many attempts have been made to engineer resveratrol production in major cereal grains but have been largely unsuccessful. In this study, we report the creation of a transgenic rice plant that accumulates 1.9 µg resveratrol/g in its grain, surpassing the previously reported anti-metabolic syndrome activity of resveratrol through a synergistic interaction between the transgenic resveratrol and the endogenous properties of the rice. Consumption of our transgenic resveratrol-enriched rice significantly improved all aspects of metabolic syndrome and related diseases in animals fed a high-fat diet. Compared with the control animals, the resveratrol-enriched rice reduced body weight, blood glucose, triglycerides, total cholesterol, and LDL-cholesterol by 24.7%, 22%, 37.4%, 27%, and 59.6%, respectively. The resveratrol-enriched rice from our study may thus provide a safe and convenient means of preventing metabolic syndrome and related diseases without major lifestyle changes or the need for daily medications. These results also suggest that future transgenic plants could be improved if the synergistic interactions of the transgene with endogenous traits of the plant are considered in the experimental design.

Topics: Acyltransferases; Adipose Tissue; Animals; Blood Glucose; Body Weight; Chromatography, High Pressure Liquid; Female; Food, Fortified; Glucosides; Glucosyltransferases; Humans; Lipids; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Oryza; Plant Leaves; Plants, Genetically Modified; Resveratrol; Seeds; Sirtuin 1; Stilbenes

The aim of this study was to investigate the association between total polyphenol intake, its subclasses (including flavonoids, phenolic acids, stilbenes and lignans), and the metabolic syndrome (MetS).. This population-based cross-sectional study was conducted on a representative of 2618 adults, aged 19 to 84 years. Dietary intake was assessed using a validated food-frequency questionnaire and intakes of total polyphenol and four main subclasses of polyphenol including flavonoids, phenolic acids, stilbenes and lignans were determined.. Higher consumption of flavonoid intakes was associated with lower odds of enlarged waist circumference, hypertriglyceridemia, low HDL cholesterol, hyperglycemia, hypertension and MetS. Subjects in the highest quartile of lignan intakes had higher odds of having hypertriglyceridemia and hyperglycemia. Subjects in the highest quartile of stilbene intakes had higher odds of having hypertension.. Intakes of selected subclasses of polyphenol such as flavonoids are associated with a lower prevalence of MetS among Tehranians.

Topics: Adult; Aged; Aged, 80 and over; Cross-Sectional Studies; Diet; Female; Flavonoids; Health Surveys; Humans; Iran; Lignans; Male; Metabolic Syndrome; Middle Aged; Polyphenols; Prevalence; Prospective Studies; Stilbenes; Urban Health; Young Adult

Resveratrol is a naturally occurring polyphenol believed to be cardioprotective. We previously demonstrated that resveratrol improves insulin signaling and glucose metabolism in liver and skeletal muscle of swine with metabolic syndrome. Although resveratrol has metabolic benefits in peripheral tissues, its effect on insulin signaling in ischemic myocardium (IM) is unclear. Therefore, we developed a clinically relevant swine model of metabolic syndrome and chronic myocardial ischemia to investigate the effects of resveratrol on insulin signaling in cardiac tissue.. Thirteen male Yorkshire swine were fed a high-cholesterol diet for 4 wk then underwent surgical placement of an ameroid constrictor to their circumflex artery to induce chronic myocardial ischemia. The high-cholesterol control group was given no drug (n = 7). The experimental group was provided the same diet and received supplemental resveratrol (100 mg/kg/d) (n = 6). Tissue was harvested 7 wk after ameroid placement for western blot and histological analyses.. In IM, there was no significant difference between the two groups in the insulin signaling markers studied. In nonischemic myocardium, there was a significant decrease in phosphorylated AMP-activated protein kinase α (P = 0.021) in the group treated with resveratrol; otherwise, there were no significant differences between the groups. Immunostaining for glucose transporter 4 and Periodic acid-Schiff staining for myocardial glycogen stores was similar between the groups.. Resveratrol has complex effects on glucose metabolism. Although prior studies demonstrated that resveratrol supplementation improves insulin sensitivity in peripheral tissues, in chronically IM, there are no significant alterations.

Topics: AMP-Activated Protein Kinases; Animals; Apoptosis; Cardiotonic Agents; Disease Models, Animal; Glucose; Insulin; Male; Metabolic Syndrome; Myocardial Ischemia; Myocardium; Resveratrol; Signal Transduction; Stilbenes; Swine

Metabolic syndrome has become an epidemic and poses tremendous burden on the health system. People with metabolic syndrome are more likely to experience cognitive decline. As obesity and sedentary lifestyles become more common, the development of early prevention strategies is critical. In this study, we explore the potential beneficial effects of a combinatory polyphenol preparation composed of grape seed extract, Concord purple grape juice extract, and resveratrol, referred to as standardized grape polyphenol preparation (SGP), on peripheral as well as brain dysfunction induced by metabolic syndrome.. We found dietary fat content had minimal effect on absorption of metabolites of major polyphenols derived from SGP. Using a diet-induced animal model of metabolic syndrome (DIM), we found that brain functional connectivity and synaptic plasticity are compromised in the DIM mice. Treatment with SGP not only prevented peripheral metabolic abnormality but also improved brain synaptic plasticity.. Our study demonstrated that SGP, comprised of multiple bioavailable and bioactive components targeting a wide range of metabolic syndrome related pathological features, provides greater global protection against peripheral and central nervous system dysfunctions and can be potentially developed as a novel prevention/treatment for improving brain connectivity and synaptic plasticity important for learning and memory.

Topics: Animals; Biological Availability; Brain; Dietary Fats; Disease Models, Animal; Female; Grape Seed Extract; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Neuronal Plasticity; Polyphenols; Rats; Rats, Sprague-Dawley; Resveratrol; Stilbenes; Synapses; Vitis

Metabolic syndrome and oxidative stress are common complications of type 2 diabetes mellitus. The present study was designed to determine whether resveratrol, a widely used nutritional supplement, can improve insulin sensitivity, metabolic complication as well as hepatic oxidative stress in fructose-fed rats. Male Sprague Dawley rats (180-200 g) were divided into four groups with 8 animals each. Fructose-fed insulin resistant group (Dia) animals were fed 65% fructose (Research diet, USA) for a period of 8 weeks, whereas control group (Con) animals were fed 65% cornstarch (Research Diet, USA). Resveratrol, 10 mg/kg/day (Dia+Resv) or metformin 300 mg/kg/day (Dia+Met) were administered orally to the 65% fructose-fed rats for 8 weeks. At the end of the feeding schedule, Dia group had insulin resistance along with increased blood glucose, triglyceride, uric acid and nitric oxide (NO) levels. Significant (p<0.05) increase in hepatic TBARS and conjugated dienes, and significant (p<0.05) decrease in hepatic SOD and vitamin C was observed in Dia group compared to Con group. Administration of metformin or resveratrol significantly (p<0.05) normalized all the altered metabolic parameters. However, a marked insulin sensitizing action was only observed in the Dia+Resv group. Similarly, while metformin administration failed to normalize the increased TBARS levels and decreased SOD activity, resveratrol showed a more promising effect of all oxidative stress parameters measured in the present study. Attenuation of hepatic oxidative stress in fructose-fed rat liver after resveratrol administration was associated with significant (p<0.05) increase in nuclear level of NRF2 compared with other groups. The present study demonstrates that resveratrol is more effective than metformin in improving insulin sensitivity, and attenuating metabolic syndrome and hepatic oxidative stress in fructose-fed rats.

Topics: Animals; Ascorbic Acid; Blood Glucose; Body Weight; Catalase; Eating; Fructose; Glucose Tolerance Test; Glutathione; Insulin; Insulin Resistance; Liver; Male; Metabolic Syndrome; Metformin; NF-E2-Related Factor 2; Nitric Oxide; Oxidative Stress; Rats; Rats, Sprague-Dawley; Resveratrol; Stilbenes; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Triglycerides; Uric Acid

Resveratrol has been shown to reverse some of the detrimental effects of metabolic syndrome (MetS). We sought to define the impact of supplemental resveratrol on normal myocardium remote from an ischemic territory in a swine model of MetS and chronic myocardial ischemia.. Yorkshire swine were fed a normal diet (control), a high cholesterol diet (HCD), or a high cholesterol diet with orally supplemented resveratrol (HCD-R; 100 mg/kg/day). Four weeks after diet modification, myocardial ischemia was induced by ameroid constrictor placement. Seven weeks later, myocardial tissue from a territory remote from the ischemia was harvested. Animals in the HCD and HCD-R groups underwent functional cardiac MRI before ischemia and before sacrifice. Tissue was harvested for protein expression analysis.. After 7 weeks of ischemia, regional left ventricular systolic function was significantly increased in HCD-R as compared with HCD animals. During ventricular pacing the HCD group had significantly decreased flow (p = 0.03); perfusion in the HCD-R was preserved as compared with the control. There was no difference in microvascular relaxation. Expression of metabolic proteins Sirt-1 (p = 0.002), AMPkinase (p = 0.02), and carnitine palmitoyltransferase-I (p = 0.002) were upregulated in the HCD-R group. Levels of protein oxidative stress were significantly increased in the HCD and HCD-R groups, as compared with the controls (p = 0.003). Activated endothelial nitric oxide synthase (eNOS) was increased in the HCD-R group (p = 0.01). There was no difference in myocardial endothelial cell density between the groups; however, dividing endothelial cells were decreased in the HCD and HCD-R groups (p = 0.006).. Resveratrol supplementation improves regional left ventricular function and preserves perfusion to myocardium remote from an area of ischemia in an animal model of metabolic syndrome and chronic myocardial ischemia.

Topics: Animals; Antioxidants; Biomarkers; Blotting, Western; Coronary Vessels; Diet, High-Fat; Disease Models, Animal; Fluorescent Antibody Technique; Heart; Magnetic Resonance Imaging; Metabolic Syndrome; Myocardial Ischemia; Myocardium; Oxidative Stress; Resveratrol; Stilbenes; Swine; Ventricular Function, Left

The purpose of this study was to examine the effects of alcohol in the context of metabolic syndrome on insulin signaling pathways in the liver and skeletal muscle.. Twenty-six Yorkshire swine were fed a hypercaloric, high-fat diet for 4 weeks then split into 3 groups: hypercholesterolemic diet alone (HCC, n = 9), hypercholesterolemic diet with vodka (HCVOD, n = 9), and hypercholesterolemic diet with wine (HCW, n = 8) for 7 weeks. Animals underwent intravenous dextrose challenge before euthanasia and tissue collection.. HCC, HCVOD, and HCW groups had similar blood fasting glucose levels, liver function test, and body mass index. Thirty and 60 minutes after dextrose infusion, HCVOD and HCW groups had significantly increased blood glucose levels compared with the HCC group. The HCW group had significantly increased levels of insulin compared with the HCC group. Immunoblotting in skeletal muscle demonstrated that alcohol up-regulates p-IRS1, IRS2, AKT, AMPKα, PPARα, Fox01, and GLUT4. In the liver, HCW had up-regulation of AKT, AMPKα, and GLUT4 compared with HCC. Skeletal muscle immunohistochemistry demonstrated increased sarcolemmal expression of GLUT4 in both alcohol groups compared with HCC.. Moderate alcohol consumption in a swine model of metabolic syndrome worsens glucose metabolism by altering activation of the insulin signaling pathway in the liver and skeletal muscle.

Topics: Alcohol Drinking; Alcoholic Beverages; Animals; Blood Glucose; Disease Models, Animal; Dose-Response Relationship, Drug; Ethanol; Glucose Transporter Type 4; Immunohistochemistry; Insulin; Insulin Receptor Substrate Proteins; Insulin Resistance; Liver; Liver Function Tests; Male; Metabolic Syndrome; Muscle, Skeletal; PPAR alpha; Resveratrol; Stilbenes; Swine; Up-Regulation

Resveratrol has been purported to modify risk factors for obesity and cardiovascular disease. We sought to examine the effects of resveratrol in a porcine model of metabolic syndrome and chronic myocardial ischemia. Yorkshire swine were fed either a normal diet (control), a high cholesterol diet (HCD), or a high cholesterol diet with supplemental resveratrol (HCD-R; 100mg/kg/day) for 11 weeks. After 4 weeks of diet modification a baseline cardiovascular MRI was performed and an ameroid constrictor was placed on the left circumflex coronary artery of each animal to induce chronic myocardial ischemia. At 7 weeks, a second cardiovascular MRI was performed and swine were sacrificed and myocardial tissue harvested. Resveratrol supplementation resulted in lower body mass indices, serum cholesterol, and C-reactive protein levels, improved glucose tolerance and endothelial function, and favorably augmented signaling pathways associated with myocardial metabolism. Interestingly, serum tumor necrosis factor-α levels were not influenced by resveratrol treatment. Immunoblotting for markers of metabolism demonstrated that insulin receptor substrate-1, glucose transporters 1 and 4, and phospho-AMPK were increased in the HCD-R group. Peroxisome proliferator-activated receptor γ and retinol binding protein 4 were downregulated in the HCD-R group as compared to the HCD group. Myocardial perfusion and function at rest as assessed with magnetic resonance imaging were not different between groups. By favorably influencing risk factors, resveratrol may decrease the burden of chronic metabolic disease and improve cardiovascular health.

Topics: Animals; Biomarkers; Cholesterol; Coronary Artery Disease; Diet; Dietary Supplements; Fatty Acids, Nonesterified; Gene Expression Regulation; Glucose Tolerance Test; Glucose Transporter Type 4; Heart; Inflammation; Insulin; Magnetic Resonance Imaging; Metabolic Syndrome; Microvessels; Muscle Cells; Myocardial Ischemia; Oxidation-Reduction; Protein Transport; Resveratrol; Risk Factors; Stilbenes; Swine

We hypothesized that supplemental resveratrol would affect glucose metabolism in the skeletal muscle and liver to improve blood glucose control.. Case-control study.. Hospital laboratory.. Yorkshire miniswine.. The swine developed metabolic syndrome by consuming a high-calorie, high–fat/cholesterol diet for 11 weeks. Pigs were fed either a normal diet (control) (n = 7), a hypercholesterolemic diet (HCC) (n = 7), or a hypercholesterolemic diet with supplemental resveratrol (100 mg/kg/d) (HCRV) (n = 7). Animals underwent dextrose challenge prior to euthanasia and tissue collection.. Measurements of glucose and insulin levels, skeletal muscle and liver protein expression, and liver function test results.. The HCC group had significantly increased blood glucose levels at 30 minutes as compared with the control and HCRV groups. The HCC group demonstrated increased fasting serum insulin levels and levels of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. Oil red O staining demonstrated increased lipid deposition in the livers of the HCC animals. Immunoblotting in the liver showed increased levels of mammalian target of rapamycin, insulin receptor substrate 1, and phosphorylated AKT in the HCRV group. Immunoblotting in skeletal muscle tissue demonstrated increased glucose transporter type 4 (Glut 4), peroxisome proliferating activation receptor coactivator 1α, peroxisome proliferator-activated receptor α, peroxisome proliferator-activated receptor , and phosphorylated AKT at threonine 308 expression as well as decreased retinol binding protein 4 in the HCRV group. Immunofluorescence staining for Glut 4 in the skeletal muscle demonstrated increased Glut 4 staining in the HCRV group compared with the HCC or control groups.. Supplemental resveratrol positively influences glucose metabolism pathways in the liver and skeletal muscle and leads to improved glucose control in a swine model of metabolic syndrome.

Topics: Animals; Blood Glucose; Case-Control Studies; Dietary Carbohydrates; Energy Intake; Energy Metabolism; Insulin; Insulin Resistance; Liver; Liver Function Tests; Metabolic Syndrome; Microscopy, Fluorescence; Muscle, Skeletal; Phytotherapy; Plant Extracts; Resveratrol; Signal Transduction; Stilbenes; Swine; Swine, Miniature; Treatment Outcome

A prenatal hypoxic insult leading to intrauterine growth restriction (IUGR) increases the susceptibility to develop metabolic syndrome (MetS) later in life. Since resveratrol (Resv), the polyphenol produced by plants, exerts insulin-sensitizing effects, we tested whether Resv could prevent deleterious metabolic effects of being born IUGR.. Pregnant rats were exposed to either a normoxic (control; 21% O(2)) or a hypoxic (IUGR; 11.5% O(2)) environment during the last third of gestation. After weaning, male offspring were randomly assigned to receive either a high-fat (HF; 45% fat) diet or an HF diet with Resv (4 g/kg diet) for 9 weeks when various parameters of the MetS were measured.. Relative to normoxic controls, hypoxia-induced IUGR offspring developed a more severe MetS, including glucose intolerance and insulin resistance, increased intra-abdominal fat deposition and intra-abdominal adipocyte size, and increased plasma triacylglycerol (TG) and free fatty acids, as well as peripheral accumulation of TG, diacylglycerol, and ceramides. In only IUGR offspring, the administration of Resv reduced intra-abdominal fat deposition to levels comparable with controls, improved the plasma lipid profile, and reduced accumulation of TG and ceramides in the tissues. Moreover, Resv ameliorated insulin resistance and glucose intolerance as well as impaired Akt signaling in the liver and skeletal muscle of IUGR offspring and activated AMP-activated protein kinase, which likely contributed to improved metabolic parameters in Resv-treated IUGR rats.. Our results suggest that early, postnatal administration of Resv can improve the metabolic profile of HF-fed offspring born from pregnancies complicated by IUGR.

Topics: Animals; Antioxidants; Body Weight; Calorimetry, Indirect; Dietary Fats; Energy Intake; Female; Fetal Growth Retardation; Hypoxia; Insulin Resistance; Male; Metabolic Syndrome; Motor Activity; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Resveratrol; Stilbenes

Sirtuins (SIRTs) are NAD(+)-dependent deacetylases that regulate metabolism and life span. We used peripheral blood mononuclear cells (PBMCs) to determine ex vivo whether insulin resistance/metabolic syndrome influences SIRTs. We also assessed the potential mechanisms linking metabolic alterations to SIRTs in human monocytes (THP-1) in vitro.. SIRT1-SIRT7 gene and protein expression was determined in PBMCs of 54 subjects (41 with normal glucose tolerance and 13 with metabolic syndrome). Insulin sensitivity was assessed by the minimal model analysis. Subclinical atherosclerosis was assessed by carotid intima-media thickness (IMT). In THP-1 cells exposed to high glucose or fatty acids in vitro, we explored SIRT1 expression, p53 acetylation, Jun NH(2)-terminal kinase (JNK) activation, NAD(+) levels, and nicotinamide phosphoribosyltransferase (NAMPT) expression. The effects of SIRT1 induction by resveratrol and of SIRT1 gene silencing were also assessed.. In vivo, insulin resistance and metabolic syndrome were associated with low PBMC SIRT1 gene and protein expression. SIRT1 gene expression was negatively correlated with carotid IMT. In THP-1 cells, high glucose and palmitate reduced SIRT1 and NAMPT expression and reduced the levels of intracellular NAD(+) through oxidative stress. No effect was observed in cells exposed to linoleate or insulin. High glucose and palmitate increased p53 acetylation and JNK phosphorylation; these effects were abolished in siRNA SIRT1-treated cells. Glucose- and palmitate-mediated effects on NAMPT and SIRT1 were prevented by resveratrol in vitro.. Insulin resistance and subclinical atherosclerosis are associated with SIRT1 downregulation in monocytes. Glucotoxicity and lypotoxicity play a relevant role in quenching SIRT1 expression.

Topics: Angiogenesis Inhibitors; Atherosclerosis; Carotid Arteries; Down-Regulation; Glucose; Glucose Tolerance Test; Humans; Insulin Resistance; Longevity; Metabolic Syndrome; Monocytes; Palmitic Acid; Reference Values; Resveratrol; Sirtuin 1; Stilbenes; Tunica Intima; Tunica Media

Resveratrol has been reported to induce angiogenesis in ischemic tissue. We hypothesized that high-dose resveratrol would improve native angiogenesis in a swine model of metabolic syndrome and chronic myocardial ischemia.. Yorkshire swine were fed a normal diet (Control, n = 7), hypercholesterolemic diet (HCD, n = 7), or hypercholesterolemic diet with supplemental resveratrol (100 mg/kg/day orally, HCD-R; n = 7) beginning 1 month prior to surgery. Chronic ischemia was created by placing an ameroid constrictor on the left circumflex coronary artery. After 7 weeks, swine underwent functional MRI, coronary angiography, and serum and heart tissue harvest for analysis.. HCD-R animals had lower body mass index (P < .001), total cholesterol (P < .001), low-density lipoprotein (LDL; P < .001), blood glucose levels (P < .001), and systolic blood pressure (P = .03) than HCD animals. There was no difference in regional myocardial function at 7 weeks (P = .25). Coronary angiograms revealed no difference in Rentrop collateral scores (P = .68). Staining for platelet endothelial cell adhesion molecule-1 demonstrated higher capillary density in the Control group (versus HCD and HCD-R; P = .02). Immunoblotting demonstrated decreased expression of the pro-angiogenic protein vascular endothelial (VE)-cadherin (P = .002) and an increase in anti-angiogenic proteins angiostatin (P = .001) and thrombospondin (P = .02) in the HCD and HCD-R groups. Matrix metalloprotease 2 (MMP 2; P = .47) and MMP 9 (P = .12) were not different among groups.. Supplemental resveratrol positively modified cardiovascular risk factors including body mass index, cholesterol, glucose tolerance, and systolic blood pressure. However, it did not increase native collateral formation in the ischemic myocardium. This may be a result of increased angiostatin and thrombospondin leading to decreased expression of VE-cadherin and other pro-angiogenic factors.

Topics: Angiogenesis Inhibitors; Angiostatins; Animals; Antigens, CD; Cadherins; Cholesterol, Dietary; Collateral Circulation; Coronary Angiography; Disease Models, Animal; Magnetic Resonance Imaging; Male; Metabolic Syndrome; Myocardial Ischemia; Neovascularization, Physiologic; Resveratrol; Stilbenes; Swine; Swine, Miniature

Resveratrol is a natural polyphenolic stilbene derivative found in several human diet components that possess important and wide-ranging effects in biological systems including anticancer, anti-inflammatory, antioxidant, cardio-protective, and anti-ageing actions and beneficial properties against metabolic diseases. This study addresses the effects of long-term administration of resveratrol on several functional alterations arising from the metabolic syndrome experimental model of obese Zucker rats, and the possible mechanisms involved. The high plasma concentrations of triglycerides, total cholesterol, free fatty acids, insulin and leptin found in obese Zucker rats were reduced in obese rats that received resveratrol. Furthermore, the elevated hepatic lipid content was significantly lower in obese rats treated with resveratrol, an effect which was related to the increased phosphorylation of 5'-AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in the liver of these animals. Resveratrol treatment also improved the inflammatory status peculiar to this model, as it increased the concentration of adiponectin and lowered tumor necrosis factor-alpha production in the visceral adipose tissue (VAT) of obese Zucker rats. Moreover, chronic intake of resveratrol enhanced VAT eNOS expression among obese Zucker rats. These effects parallel the activation of AMPK and inhibition by phosphorylation of ACC in this tissue. The raised systolic blood pressure and reduced aortic eNOS expression found in obese Zucker rats were significantly improved in the resveratrol-treated obese rats. In conclusion, resveratrol improved dyslipidemia, hyperinsulinemia, hyperleptinemia and hypertension in obese Zucker rats, and produced anti-inflammatory effects in VAT, effects that seem to be mediated by AMPK activation.

Topics: Adipose Tissue; Animals; Blood Pressure; Disease Models, Animal; Drug Administration Schedule; Humans; Hypertension; Lipid Metabolism; Male; Metabolic Syndrome; Obesity; Random Allocation; Rats; Rats, Zucker; Resveratrol; Stilbenes