stilbenes and Metabolic-Diseases

Vascular metabolic dysfunction presents in various diseases, such as atherosclerosis, hypertension, and diabetes mellitus. Due to the high prevalence of these diseases, it is important to explore treatment strategies to protect vascular function. Resveratrol (RSV), a natural polyphenolic phytochemical, is regarded as an agent to regulate metabolic pathways. Many studies have proven that RSV has beneficial effects on improving metabolism in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), which provide new directions to treat vascular metabolic diseases. Herein, we overviewed that RSV could regulate cell metabolism activity by inhibiting glucose uptake, suppressing glycolysis, preventing cells from fatty acid-related damages, reducing lipogenesis, increasing fatty acid oxidation, enhancing lipolysis, elevating uptake and synthesis of glutamine, and increasing NO release. Furthermore, in clinical trials, although the results from different studies remain controversial, we proposed that RSV had better therapeutic effects at high concentrations and for patients with metabolic disorders.

Topics: Endothelial Cells; Fatty Acids; Humans; Lipid Metabolism; Metabolic Diseases; Resveratrol; Stilbenes; Vascular Diseases

Alcohol abuse is associated with numerous health problems, including metabolic disturbances and liver damage. Therefore, different compounds are continuously being tested to evaluate their potential effectiveness in reducing these harmful changes. Animal studies clearly show that resveratrol is capable of ameliorating some consequences of ethanol ingestion. Resveratrol is a naturally occurring diphenolic compound having pleiotropic, health-promoting properties. Its beneficial action have been also demonstrated in animal models with ethanol-induced metabolic disturbances and liver injury. In ethanol treated animals, resveratrol effectively reduced liver lipid accumulation. Moreover, this compound diminished necrosis of hepatocytes, and also reduced liver fibrosis. The hepatoprotective action of resveratrol is largely associated with its ant-oxidant and anti-inflammatory properties, and also covers changes in activities of some enzymes. It is known that this compound upregulates the adiponectin-SIRT1-AMPK signaling pathway in the liver. Resveratrol was also found to positively affect blood lipids in animals exposed to ethanol. Moreover, administration of resveratrol to animals with ethanol-induced hypoinsulinemia and insulin resistance was shown to alleviate these disturbances. These outcomes clearly indicate that resveratrol holds great potential to reduce some consequences of ethanol ingestion. However, human studies are required to fully assess its therapeutic value.

Topics: Animals; Antioxidants; Ethanol; Humans; Lipid Metabolism; Liver; Liver Diseases; Metabolic Diseases; Resveratrol; Stilbenes

Metabolic disease comprises a set of risk factors highly associated with obesity and insulin resistance and is a consequence of central adiposity, hyperglycemia, and dyslipidemia. Furthermore, obesity increases the risk of the development of metabolic disease due to ectopic fat deposition, low-grade inflammation, and systemic energy disorders caused by dysregulated adipose tissue function. Piceatannol is a naturally occurring polyphenolic stilbene found in various fruits and vegetables and has been reported to exhibit anticancer and anti-inflammatory properties. In addition, recently reported beneficial effects of piceatannol on hypercholesterolemia, atherosclerosis, and angiogenesis underscore its therapeutic potential in cardiovascular disease. However, investigation of its role in metabolic disease is still in its infancy. This review intensively summarizes in vitro and in vivo studies supporting the potential therapeutic effects of piceatannol in metabolic disease, including inhibition of adipogenesis and lipid metabolism in adipocytes, and regulation of hyperlipidemia, hyperglycemia, insulin resistance, and fatty acid-induced inflammation and oxidative stress.

Topics: Animals; Humans; Metabolic Diseases; Plant Extracts; Stilbenes

Cardiovascular diseases, especially ischemic heart disease and cardiometabolic disease, remain to be the leading cause of morbidity and mortality worldwide. Despite recent progress in diagnostic and therapeutic approaches, the incidence of cardiovascular disease is still rising. Therefore, alternative favorable treatment is urgently needed to rescue the fast growing numbers of patients.. Herein we aimed to review the relevant role and explore the possibility of SIRT1 as a promising target for protection of heart from ischemia/reperfusion injury and cardiometabolic diseases.. The activation of SIRT1 participates in a variety of important metabolic and physiologic processes including stress resistance, metabolism, apoptosis and energy balance in heart ischemia injury and cardiometabolic disease.. Current medication targeting SIRT1 may represent a new therapeutic trend for the prevention of cardiovascular disease that is related to energy balance and metabolism.

Topics: Animals; Apoptosis; Disease Models, Animal; Heterocyclic Compounds, 4 or More Rings; Humans; Metabolic Diseases; Molecular Targeted Therapy; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocytes, Cardiac; Resveratrol; Sirtuin 1; Stilbenes; Transcriptional Activation

The suggested health effects (e.g., disease prevention) of dietary bioactive compounds such as resveratrol are challenging to prove in comparison to man-made drugs developed for therapeutic purposes. Dietary bioactive compounds have multiple cellular targets and therefore have a variety of biological effects. Extrapolating the biological effects of dietary compounds from in vitro and in vivo animal experiments to humans may lead to over- or under-estimation of the effect and role of these compounds. The present paper will discuss a few of these challenges and suggest directions for future research. Questions we address include: (1) Is the combinatorial effect of resveratrol and other compounds real? (2) What are the real and relevant doses of resveratrol after administration? and (3) Is it possible to estimate the preventive effect of resveratrol by clinical trials using standard experimental designs? The examples concerning resveratrol taken from the scientific literature are mainly from 2010 and later. The challenges pointed out in this review are similar to most naturally occurring bioactive compounds.

Topics: Alzheimer Disease; Animals; Antioxidants; Biological Availability; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Humans; Metabolic Diseases; Neoplasms; Phytochemicals; Randomized Controlled Trials as Topic; Resveratrol; Stilbenes

Resveratrol is a naturally occurring stilbene endowed with multiple health-promoting effects. It is produced by certain plants including several dietary sources such as grapes, apples, raspberries, blueberries, plums, peanuts, and products derived therefrom (e.g., wine). Resveratrol can be isolated and purified from these biological sources or synthesized in a few steps with an overall high yield. This compound and its glucoside, the trans-polydatin piceid, have received worldwide attention for their beneficial effects on cardiovascular, inflammatory, neurodegenerative, metabolic, and age-related diseases. These health-promoting effects are particularly attractive given the prevalence of resveratrol-based nutraceuticals and the paradoxical epidemiologic observation that wine consumption is inversely correlated to the incidence of coronary heart disease. However, the notion of resveratrol as a "magic bullet" was recently challenged by clinical trials showing that this polyphenol does not have a substantial influence on health status and mortality risk. In the present review, we discuss the proposed therapeutic attributes and the mode of molecular actions of resveratrol. We also cover recent pharmacologic efforts to improve the poor bioavailability of resveratrol and influence the transition between body systems in humans. We conclude with some thoughts about future research directions that might be meaningful for resolving controversies surrounding resveratrol.

Topics: Coronary Disease; Diet; Dietary Supplements; Fruit; Glycosides; Humans; Inflammation; Metabolic Diseases; Neurodegenerative Diseases; Phytotherapy; Plant Extracts; Polyphenols; Resveratrol; Stilbenes; Wine

The grape antioxidant resveratrol has been a topic of intense research for the past three decades. Resveratrol and other grape ingredients, as well as whole-grape products, have shown considerable promise in health promotion and disease management. Phytochemically, whole grape represents a natural combination of resveratrol and other phytonutrients, as it contains several catechins, anthocyanins, polyphenols, and flavonols. Thus, whole grape products or specific combinations of grape constituents provide us with the possibility of synergistic interactions leading to improved efficacy. Recent research has suggested that whole-grape products may help in maintaining heart health and protect against aging, aging-associated diseases, neurodegeneration, and some cancers. On the basis of available recent literature, the grape fruit or whole-grape products seem to be safer choices for better health and disease prevention. However, for advanced disease conditions, individual grape ingredients (such as resveratrol) or combinations of multiple ingredients, together with existing therapies, appear to be better approaches. Further clinical studies are needed to understand the benefits of grapes and their products in the prevention and management of specific diseases.

Topics: Animals; Cardiovascular Diseases; Clinical Trials as Topic; Diet; Disease Management; Fruit; Humans; Metabolic Diseases; Resveratrol; Stilbenes; Vitis

Resveratrol is a phenolic phytochemical, with a stilbene backbone, derived from edible plants such as grape and peanut. It is a bioactive molecule with physiological effects on multiple organ systems. Its effects range from the neuroprotective to the nephroprotective, including cardiovascular, neuronal, and antineoplastic responses as a part of its broad spectrum of action. In this review, we examine the effects of resveratrol on the following organ systems: the central nervous system, including neurological pathology such as Parkinson's and Alzheimer's disease; the cardiovascular system, including disorders such as atherosclerosis, ischemia-reperfusion injury, and cardiomyocyte hypertrophy; the kidneys, including primary and secondary nephropathies and nephrolithiasis; multiple forms of cancer; and metabolic syndromes including diabetes. We emphasize commonalities in extracellular matrix protein alterations and intracellular signal transduction system induction following resveratrol treatment. We summarize the known anti-inflammatory, antioxidative, and cytoprotective effects of resveratrol across disparate organ systems. Additionally, we analyze the available literature regarding the pharmacokinetics of resveratrol formulations used in these studies. Finally, we critically examine select clinical trials documenting a lack of effect following resveratrol treatment.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Cardiovascular Diseases; Central Nervous System; Humans; Kidney Diseases; Metabolic Diseases; Neuroprotective Agents; Resveratrol; Sirtuin 1; Stilbenes

When energy supply is low, organisms respond by slowing aging and increasing resistance to diverse age-related pathologies. Targeting the mechanisms underpinning this response may therefore treat multiple disorders through a single intervention. Here, we discuss AMP-activated protein kinase (AMPK) as an integrator and mediator of several pathways and processes linking energetics to longevity. Activated by low energy, AMPK is both prolongevity and druggable, but its role in some pathologies may not be beneficial. As such, activating AMPK may modulate multiple longevity pathways to promote healthy aging, but unlocking its full potential may require selective targeting toward substrates involved in longevity assurance.

Topics: Aging; AMP-Activated Protein Kinases; Animals; Aspirin; Energy Metabolism; Humans; Metabolic Diseases; Metformin; Mitochondria; Neoplasms; Resveratrol; Stilbenes

In the search for novel preventive and therapeutic modalities in the management of metabolic diseases and obesity, resveratrol has attracted great attention over the past decades. Preclinical trials suggest that resveratrol mimics the metabolic effects of calorie restriction (CR) via activation of silent mating type information regulation 2 homolog 1 (SIRT1). In experimental animals, this potential translates into prevention or improvement of glucose metabolism, anti-inflammation, cancer, and nonalcoholic fatty liver disease. Moreover, and in accordance with CR, supplementation with resveratrol promotes longevity in several primitive species and protects against diet-induced metabolic abnormalities in rodents. Despite the substantial preclinical evidence, human clinical data are very scarce, and even though the compound is widely distributed as an over-the-counter human nutritional supplement, its therapeutic rationale has not been well characterized. In this review, we provide a brief overview of the field and discuss the future scientific directions of resveratrol research.

Topics: Animals; Caloric Restriction; Clinical Trials as Topic; Dietary Supplements; Energy Metabolism; Humans; Metabolic Diseases; Obesity; Resveratrol; Sirtuin 1; Stilbenes

Resveratrol-a natural polyphenolic compound-was first discovered in the 1940s. Although initially used for cancer therapy, it has shown beneficial effects against most cardiovascular and cerebrovascular diseases. A large part of these effects are related to its antioxidant properties. Here we review: (a) the sources, the metabolism, and the bioavailability of resveratrol; (b) the ability of resveratrol to modulate redox signalling and to interact with multiple molecular targets of diverse intracellular pathways; (c) its protective effects against oxidative damage in cardio-cerebro-vascular districts and metabolic disorders such as diabetes; and (d) the evidence for its efficacy and toxicity in humans. The overall aim of this review is to discuss the frontiers in the field of resveratrol's mechanisms, bioactivity, biology, and health-related use.

Topics: Antioxidants; Biological Availability; Cardiovascular Diseases; Cerebrovascular Disorders; Clinical Trials as Topic; Diabetes Mellitus; Humans; Metabolic Diseases; Oxidation-Reduction; Oxidative Stress; Resveratrol; Stilbenes

Metabolic diseases, such as insulin resistance, type II diabetes, and obesity, are associated with a low-grade chronic inflammation (inflammatory stress), oxidative stress, and endoplasmic reticulum (ER) stress. Because the integration of these stresses is critical to the pathogenesis of metabolic diseases, agents and cellular molecules that can modulate these stress responses are emerging as potential targets for intervention and treatment of metabolic diseases. It has been recognized that heme oxygenase-1 (HO-1) plays an important role in cellular protection. Because HO-1 can reduce inflammatory stress, oxidative stress, and ER stress, in part by exerting antioxidant, anti-inflammatory, and antiapoptotic effects, HO-1 has been suggested to play important roles in pathogenesis of metabolic diseases. In the present review, we will explore our current understanding of the protective mechanisms of HO-1 in metabolic diseases and present some emerging therapeutic options for HO-1 expression in treating metabolic diseases, together with the therapeutic potential of curcumin and resveratrol analogues that have their ability to induce HO-1 expression.

Topics: Animals; Curcumin; Enzyme Induction; Heme Oxygenase-1; Humans; Metabolic Diseases; Resveratrol; Stilbenes

Cascade of youth? Resveratrol, the celebrated phytoalexin of red wine, was known to activate AMPK indirectly, but how this happened was unclear. In a paper recently published in Cell, S.-J. Park, J. H. Chung and co-workers identify the signalling cascade, which begins with the inhibition of phosphodiesterases, in particular PDE4. But questions remain, even while new perspectives open up.

Topics: Health; Humans; Metabolic Diseases; Resveratrol; Signal Transduction; Stilbenes

Resveratrol is a polyphenolic flavonoid found in a diversity of plants, especially berry fruits and is a popular nutritional supplement. It is known to have antioxidant, anti-inflammatory, and anticarcinogenic properties. Recently, additional evidence has been found that resveratrol is beneficial to metabolic and cardiovascular health and may increase the life expectancy of various organisms. These biological effects are widely believed to be due to the ability of resveratrol to activate silent mating-type information regulation 2 homolog 1, a nicotinamide adenine dinucleotide-dependent deacetylase. However, other research has shown that 5'-adenosine monophosphate-activated kinase and not silent mating-type information regulation 2 homolog 1 may be the target of resveratrol. A recent study reported that resveratrol directly inhibits cyclic adenosine monophosphate-specific phosphodiesterases and then activates 5'-adenosine monophosphate-activated kinase. Therefore, the mechanism underlying the diverse nutritional and therapeutic activities of resveratrol needs to be further explored. Furthermore, the optimal dose and possible adverse effects of resveratrol in humans are completely clear. The purpose of this review is to present some of the newly discovered biological effects of resveratrol, including autophagy and stem cell regulation, and research opportunities for the application of resveratrol in cardiovascular and metabolic health. Described herein is the recent understanding of the mechanism of action of resveratrol and future research directions to ascertain the potential of this flavonoid that is present in food.

Topics: AMP-Activated Protein Kinases; Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Autophagy; Cardiovascular Diseases; Disease Models, Animal; Humans; Metabolic Diseases; Resveratrol; Signal Transduction; Sirtuin 1; Stilbenes

Sirtuins represent a novel family of enzymes that are collectively well situated to help regulate nutrient sensing and utilization, metabolic rate and ultimately metabolic disease. Activation of one of these enzymes, SIRT1, leads to enhanced activity of multiple proteins, including peroxisome-proliferator activated receptor coactivator-1alpha (PGC-1alpha), which helps to mediate some of the in vitro and in vivo effects of sirtuins. As such, enhanced SIRT1 activity decreases glucose levels, improves insulin sensitivity, increases mitochondrial number and function, decreases adiposity, improves exercise tolerance and potentially lowers body weight. SRT-501 is a proprietary formulation of resveratrol with improved bioavailability. As such, SRT-501 represents the first in a novel class of SIRT1 activators that has proven to be safe and well-tolerated in humans. Clinical trials in type 2 diabetic patients are currently underway.

Topics: Base Sequence; Diabetes Mellitus, Type 2; Energy Metabolism; Enzyme Activators; Enzyme Inhibitors; Humans; Metabolic Diseases; Molecular Sequence Data; Molecular Structure; Obesity; Resveratrol; Sirtuin 1; Sirtuins; Stilbenes

The lack of effective Alzheimer's disease treatment is becoming a challenge for researchers and prompts numerous attempts to search for and develop better therapeutic solutions. Compounds that affect several routes of the neurodegeneration cascade leading to the development of disease are of particular interest. An example of such substances is resveratrol and its synthetic and natural derivatives, which have gained popularity in recent years and show promise as a possible new therapeutic option in the approach to Alzheimer's disease treatment. In this article, the state of the art evidence on the role of resveratrol (RSV) in neuroprotection is presented; research results are summarized and the importance of resveratrol and its derivatives in the treatment of Alzheimer's disease are underlined. It also focuses on various modifications of the resveratrol molecule that should be taken into account in the design of future research on drugs against Alzheimer's disease.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Benzofurans; Blood-Brain Barrier; Central Nervous System Diseases; Humans; Inflammation; Metabolic Diseases; Neuroprotection; Oxidative Stress; Resveratrol; Stilbenes; tau Proteins

Abdominal obesity is recognized as the main reason of metabolic syndrome, which is closely related to disordered skeletal and/or abdominal muscle metabolic functions. Metabolomics is a comprehensive assessment system in biological metabolites. The aim of our present study is to investigate the diet-induced metabolic risk factors by metabolic in the abdominal muscles and clarify the relationship between atheroprotective effects of Resveratrol (Rev) and abdominal muscles metabolic components during the development of atherosclerosis.. The mice were randomly divided into three groups including normal group (N), high fat diet (HFD or H) group and high fat diet with Rev treated group (HR). GC-MS combined with pattern recognition approaches were employed to obtain comprehensive metabolic signatures and related differential metabolites after 24 week HFD feeding. Oil Red O staining and Electron microscopy technology (EMT) were employed to detect the size of fatty plaques and intracellular lipid accumulation, respectively.. The result indicated that 22 types of metabolites in the abdominal muscles were obviously altered by HFD feeding group. Moreover, Rev treatment obviously increased 11 different kinds of metabolites, most of which were involved in the carbohydrate, amino acid and lipid metabolisms. Importantly, these elevated different metabolites were involved in pathways mainly related to galactose metabolism, alanine, aspartate and glutamate metabolism, glyoxylate and dicarboxylate metabolism in abdominal muscles. Oil Red O staining and Electron microscopy showed less lipid accumulation in the lesions and decreased intracellular lipid deposition in the foam cells in HR group.. We concluded that Rev produced a beneficial effect partially by modulating multiple metabolism pathways and metabolites in the abdominal muscles, which may provide a new protective mechanism of Rev on the progression of atherosclerosis. These notably changed metabolites might be potential biomarkers or therapeutic targets during development of metabolic syndrome and atherosclerosis.

Topics: Abdominal Muscles; Amino Acids; Animals; Apolipoproteins E; Atherosclerosis; Carbohydrate Metabolism; Diet, High-Fat; Discriminant Analysis; Gas Chromatography-Mass Spectrometry; Least-Squares Analysis; Lipid Metabolism; Lipids; Metabolic Diseases; Mice; Mice, Knockout; Microscopy, Electron; Monosaccharides; Resveratrol; Risk Factors; Stilbenes

Protein restriction in pregnancy produces maternal and offspring metabolic dysfunction potentially as a result of oxidative stress. Data are lacking on the effects of inhibition of oxidative stress. We hypothesized that maternal resveratrol administration decreases oxidative stress, preventing, at least partially, maternal low protein-induced maternal and offspring metabolic dysfunction. In the present study, pregnant wistar rats ate control (C) (20% casein) or a protein-restricted (R) (10% casein) isocaloric diet. Half of each group received resveratrol orally, 20 mg kg(-1) day(-1), throughout pregnancy. Post-delivery, mothers and offspring ate C. Oxidative stress biomarkers and anti-oxidant enzymes were measured in placenta, maternal and fetal liver, and maternal serum corticosterone at 19 days of gestation (dG). Maternal (19 dG) and offspring (postnatal day 110) glucose, insulin, triglycerides, cholesterol, fat and leptin were determined. R mothers showed metabolic dysfunction, increased corticosterone and oxidative stress and reduced anti-oxidant enzyme activity vs. C. R placental and fetal liver oxidative stress biomarkers and anti-oxidant enzyme activity increased. R offspring showed higher male and female leptin, insulin and corticosterone, male triglycerides and female fat than C. Resveratrol decreased maternal leptin and improved maternal, fetal and placental oxidative stress markers. R induced offspring insulin and leptin increases were prevented and other R changes were offspring sex-dependent. Resveratrol partially prevents low protein diet-induced maternal, placental and sex-specific offspring oxidative stress and metabolic dysfunction. Oxidative stress is one mechanism programming offspring metabolic outcomes. These studies provide mechanistic evidence to guide human pregnancy interventions when fetal nutrition is impaired by poor maternal nutrition or placental function.

Topics: Animals; Antioxidants; Female; Insulin; Leptin; Liver; Male; Metabolic Diseases; Oxidative Stress; Placenta; Pregnancy; Prenatal Exposure Delayed Effects; Prenatal Nutritional Physiological Phenomena; Protein Deficiency; Rats; Rats, Wistar; Resveratrol; Sex Factors; Stilbenes

Consumption of high-fat diet (HFD) is related with increased oxidative stress and dysfunctional mitochondria in many organs. The effects of resveratrol (trans-3,5,4'-trihydroxystilbene) that can protect T lymphocytes in various disease conditions on the HFD-induced apoptosis of CD4(+) CD25(+) CD127(low/-) regulatory T cells (Tregs) were studied, and the possible mechanism was postulated. Resveratrol significantly decreased Tregs death induced by 20-wk HFD, being associated with the reduction of reactive oxygen species production and the alleviation of HFD-induced loss of mitochondrial membrane potential (Δψm) in Tregs. Furthermore, resveratrol increased the expression of factors that regulated mitochondrial biogenesis in Tregs. Finally, resveratrol recovered the HFD-induced activation of apoptotic markers in Tregs. Resveratrol protected Tregs against HFD-induced apoptosis by reducing oxidative stress, restoring mitochondrial functional activities, and stimulating mitochondrial biogenesis.

Topics: Animals; Antioxidants; Apoptosis; Diet, High-Fat; Drug Evaluation, Preclinical; Male; Membrane Potential, Mitochondrial; Metabolic Diseases; Mice; Mice, Inbred C57BL; Mitochondria; Mitochondrial Turnover; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Resveratrol; Stilbenes; T-Lymphocytes, Regulatory

The aim of this study was to evaluate the effect of smokeless tobacco extract on ovariectomized female rats and to investigate the role of resveratrol in alleviating associated vascular and diabetic complications.. Thirty-six female Wistar rats (8 wk old) were subjected to bilateral ovariectomy (OVX) or sham operation and randomly assigned to six groups: sham operation; OVX; OVX + aqueous extract of smokeless tobacco (AEST); OVX + AEST + 17β-estradiol; OVX + AEST + resveratrol 25 mg/kg/day PO; and OVX + AEST + resveratrol 50 mg/kg/day PO. All treatments were given for 60 days. Various vascular and metabolic markers (such as serum glucose, triglycerides, cholesterol, insulin, estradiol, glycosylated hemoglobin, glucose tolerance), ex vivo vascular reactivity of aortic ring, and aortic collagen levels were estimated after the treatments.. Oral exposure to smokeless tobacco extract in ovariectomized female rats triggered a significant increase in metabolic markers (viz, serum triglycerides, cholesterol, glucose, insulin, glycosylated hemoglobin), and aortic collagen levels. It also led to decreased serum nitrate-nitrite levels and vascular reactivity. Resveratrol 50 mg/kg/day PO attenuated detrimental changes in aortic reactivity and aortic collagen levels, improved glucose tolerance, and reversed the deleterious effects on other serum parameters comparable to 17β-estradiol.. Resveratrol treatment for 60 days abrogates the deleterious effects of smokeless tobacco on ovariectomized female rats. Resveratrol in adequate doses can be effectively used as an alternative to estrogen therapy for smokeless tobacco-induced vascular and diabetic complications.

Topics: Animals; Aorta; Collagen; Diabetes Complications; Diabetes Mellitus; Estradiol; Female; Glucose Tolerance Test; Insulin; Metabolic Diseases; Nitrates; Nitrites; Ovariectomy; Rats; Rats, Wistar; Resveratrol; Stilbenes; Tobacco, Smokeless; Vascular Diseases

Diabetes mellitus (DM) is characterized by dysregulated energy metabolism. Resveratrol (RSV) has been shown to ameliorate hyperglycemia and hyperlipidemia in diabetic animals. However, its overall in vivo effects on energy metabolism and the underlying mechanism require further investigation. In the present study, electrospray ionization-tandem mass spectrometry was employed to characterize the urine and plasma metabolomes of control, streptozotocin-induced DM and RSV-treated DM rats. Using principal component analysis (PCA) and heat map analysis, we discovered significant differences among control and experimental groups. RSV treatment significantly reduced the metabolic abnormalities in DM rats. Compared with the age-matched control rats, the level of carnitine was lower, and the levels of acetylcarnitine and butyrylcarnitine were higher in the urine and plasma of DM rats. RSV treatment ameliorated the deranged carnitine metabolism in DM rats. In addition, RSV treatment attenuated the diabetic ketoacidosis and muscle protein degradation, as evidenced from the attenuation of elevated urinary methyl-histidine and plasma branched-chain amino acids levels in DM rats. The beneficial effects of RSV in DM rats were correlated with activation of hepatic AMP-activated protein kinase and SIRT1 expression, increase of hepatic and muscular mitochondrial biogenesis and inhibition of muscle NF-κB activities. We concluded that RSV possesses multiple beneficial metabolic effects in insulin-deficient DM rats, particularly in improving energy metabolism and reducing protein wasting.

Topics: Adenylate Kinase; Animals; Antioxidants; Cytokines; Diabetes Mellitus, Experimental; Drug Evaluation, Preclinical; Male; Metabolic Diseases; Models, Biological; Muscle, Skeletal; Muscular Diseases; NF-kappa B; Rats; Rats, Sprague-Dawley; Resveratrol; Sirtuin 1; Stilbenes; Streptozocin; Wasting Syndrome

Topics: Adipocytes; Alcohol Drinking; Antioxidants; Cardiovascular Diseases; Humans; Metabolic Diseases; Platelet Aggregation Inhibitors; Resveratrol; Stilbenes; Wine

SIRT1, a NAD(+)-dependent protein deacetylase that regulates transcription factors involved in key cellular processes, has been implicated as a mediator of the beneficial effects of calorie restriction. In a recent issue of Nature, Milne et al. (2007) describe novel potent activators of SIRT1, whose administration to insulin-resistant animals improves glucose homeostasis.

Topics: Animals; Antioxidants; Humans; Metabolic Diseases; Models, Biological; Resveratrol; Sirtuin 1; Sirtuins; Stilbenes

Diminished mitochondrial oxidative phosphorylation and aerobic capacity are associated with reduced longevity. We tested whether resveratrol (RSV), which is known to extend lifespan, impacts mitochondrial function and metabolic homeostasis. Treatment of mice with RSV significantly increased their aerobic capacity, as evidenced by their increased running time and consumption of oxygen in muscle fibers. RSV's effects were associated with an induction of genes for oxidative phosphorylation and mitochondrial biogenesis and were largely explained by an RSV-mediated decrease in PGC-1alpha acetylation and an increase in PGC-1alpha activity. This mechanism is consistent with RSV being a known activator of the protein deacetylase, SIRT1, and by the lack of effect of RSV in SIRT1(-/-) MEFs. Importantly, RSV treatment protected mice against diet-induced-obesity and insulin resistance. These pharmacological effects of RSV combined with the association of three Sirt1 SNPs and energy homeostasis in Finnish subjects implicates SIRT1 as a key regulator of energy and metabolic homeostasis.

Topics: Acetylation; Adult; Animals; Dietary Fats; Energy Metabolism; Gene Expression Regulation; Humans; Insulin Resistance; Male; Metabolic Diseases; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mitochondria, Muscle; Motor Activity; Muscle Fibers, Skeletal; Obesity; Oxidative Phosphorylation; Oxygen Consumption; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Polymorphism, Single Nucleotide; Resveratrol; Sirtuin 1; Sirtuins; Specific Pathogen-Free Organisms; Stilbenes; Trans-Activators; Transcription Factors