stilbenes and Weight-Loss

Obesity and metabolic syndrome are significant global health issues, with current public health messages predominately focused on altering dietary and physical activity behaviors. Resveratrol is a polyphenol (stilbenoid) commonly found in grapes, and human trials to date have shown conflicting and limited beneficial effects with respect to health. The aim of this study was to determine the effect of resveratrol supplementation on reducing body weight and modifying associated inflammatory markers.. A systematic review was undertaken following the PRISMA guidelines and using five indexed databases (OVID MEDLINE, Cochrane Library, Web of Science, SCOPUS, and CINAHL). A search strategy was formulated to select randomized, double-blind, placebo-controlled human trials investigating the effects of resveratrol supplementation on obesity or overweight, including body weight, metabolic and inflammatory markers.. Five thousand five hundred sixty-nine studies published from 1990 to November 2015 were identified, with only nine papers meeting the inclusion criteria. The studies involved 208 participants (aged 49.2 ± 8.3 years) and utilized a substantial range of resveratrol doses (75-3000 mg/day). Study durations were a minimum of 2 weeks (14-90 days). Seven studies indicated no significant change in body mass index or body weight (P > 0.05), and three studies showed no improvements in fat mass, fat volume, or abdominal fat distribution (P > 0.05). Four studies included measurements of inflammatory markers, with three of these finding resveratrol supplementation to have a significant positive effect (P > 0.05).. Based on the included studies, there is currently insufficient evidence to support the recommendation of resveratrol supplements in management of obesity. However, there were significant but not entirely consistent anti-inflammatory effects after resveratrol supplementation in overweight and obese individuals.

Topics: Anti-Inflammatory Agents; Dietary Supplements; Humans; Obesity; Overweight; Randomized Controlled Trials as Topic; Resveratrol; Stilbenes; Weight Loss

To evaluate the efficacy of an orlistat-resveratrol (O-R) combination in subjects with obesity over a 6-month period.. This study was a double-blind, parallel, randomized controlled clinical trial. Patients fulfilling the selection criteria (age from 20 to 60 years and body mass index (BMI) ≥30 and ≤39.9 kg/m(2) ) consumed an energy-reduced diet with 500 fewer calories than their usual diet for 2 weeks. Then the participants were randomly assigned to four groups, placebo, resveratrol, orlistat, or O-R, and they consumed the energy-reduced diet for 6 months. The study consisted of seven visits. During each visit, a 24-h recall was performed, along with measurements of anthropometric and serum biochemical parameters.. A total of 161 participants were selected. Of these, 84 participants completed the study. A significant weight loss of -6.82 kg (95% CI -8.37 to -5.26) was observed in the O-R group compared with -3.50 kg (-5.05 to -1.95, P = 0.021) in the placebo group. In contrast, the -6.02 kg (-7.68 to -4.36) orlistat and -4.68 kg (-6.64 to -2.71) resveratrol monotherapy losses did not significantly differ from the placebo. Significant decreases in BMI, waist circumference, fat mass, triglycerides, leptin, and leptin/adiponectin ratio were observed with the O-R combination.. The O-R combination was the most effective weight loss treatment.

Topics: Adult; Aged; Anthropometry; Anti-Obesity Agents; Body Mass Index; Caloric Restriction; Diet; Double-Blind Method; Drug Therapy, Combination; Energy Intake; Female; Humans; Lactones; Leptin; Male; Mexico; Middle Aged; Obesity; Orlistat; Placebos; Resveratrol; Stilbenes; Treatment Outcome; Triglycerides; Weight Loss

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

Cancer-associated cachexia (CAC) is the nutrition-independent loss of lean muscle and adipose tissues, and results in reduced chemotherapy effectiveness and increased mortality. Preventing adipose loss is considered a key target in the early stages of cachexia. Lipolysis is considered the central driver of adipose loss in CAC. We recently found that piceatannol, but not its analogue resveratrol, exhibits an inhibitory effect on lipolysis. The objective of this study was to investigate the role of piceatannol in cancer-associated lipolysis and cachexia-induced weight loss. Cancer cell-induced lipolysis in adipocytes was stimulated using cancer-conditioned media (CCM) or co-culture with human pancreatic cancer cells and the cachexia-associated cytokines TNF-α and interleukin-6 in 3T3-L1 adipocytes. C26 colon carcinoma-bearing mice were modeled using CAC

Topics: Adipose Tissue; Animals; Cachexia; Colonic Neoplasms; Culture Media, Conditioned; Cytokines; Lipolysis; Mice; Neoplasms; Polyphenols; Stilbenes; Weight Loss

Exercise and resveratrol supplementation exhibit anti-obesity functions in the long term but have not been fully investigated yet in terms of their early potential effectiveness. Mice fed with high-fat diet were categorized into control (Cont), exercise (Ex), resveratrol supplementation (Res), and exercise combined with resveratrol supplementation (Ex ＋ Res) groups. In the four-week period of weight loss, exercise combined with resveratrol supplementation exerted no additional effects on body weight loss but significantly improved whole-body glucose and lipid homeostasis. The combined treatment significantly decreased intrahepatic lipid content but did not affect intramyocellular lipid content. Moreover, the treatment significantly increased the contents of mtDNA and cytochrome c, the expression levels of peroxisome proliferator-activated receptor gamma coactivator-1 alpha and its downstream transcription factors, and the activities of ATPase and citrate synthase. However, exercise, resveratrol, and their combination did not promote myofiber specification toward slow-twitch type. The effects of exercise combined with resveratrol supplementation on weight loss could be partly due to enhanced mitochondrial biogenesis and not to fiber-type shift in skeletal muscle tissues. [BMB Reports 2018; 51(4): 200-205].

Topics: Animals; Diet, High-Fat; Glucose; Homeostasis; Lipids; Male; Mice; Mice, Inbred ICR; Mice, Obese; Muscle, Skeletal; Obesity; Physical Conditioning, Animal; Resveratrol; Stilbenes; Transcription Factors; Weight Loss

This experiment was aimed at elucidating the protective effect of resveratrol against diabetes. Forty male Wistar albino rats were allocated into four groups: the control and streptozotocin (STZ)-induced diabetes groups were treated either with placebo (1 ml/kg, i.p.) or resveratrol (20 mg/kg, i.p.) for 8 weeks. Body weight, blood glucose and serum malondialdehyde (MDA) concentrations were monitored. At the end of the experimental period, expression levels of visfatin, sirtuin-1 (SIRT1) and glucose transporters (GLUTs, 2 and 4) were measured in skeletal muscle and pancreas by Western blotting. The resveratrol treatment partially compensated for body weight loss and alleviated hyperglycaemia and returned serum MDA concentrations to the control group levels. Data suggest that supplementation may reduce the severity of diabetes and its complications through suppressing oxidative stress and increasing potential to internalise glucose by extrahepatic tissues.

Topics: Animals; Antioxidants; Blood Glucose; Diabetes Mellitus, Experimental; Dietary Supplements; Glucose Transport Proteins, Facilitative; Hyperglycemia; Hypoglycemic Agents; Male; Malondialdehyde; Muscle, Skeletal; Nicotinamide Phosphoribosyltransferase; Oxidative Stress; Pancreas; Phytotherapy; Plant Extracts; Polyphenols; Rats, Wistar; Resveratrol; Sirtuin 1; Stilbenes; Weight Loss

Resveratrol, a naturally occurring polyphenol has received significant attention as a potent anti-inflammatory agent. Inflammatory bowel disease (IBD) is a chronic intestinal inflammation caused by hyperactivated effector immune cells that produce proinflammatory cytokines. Myeloid derived suppressor cells (MDSCs) are a heterogeneous population characterized by the co-expression of CD11b(+) and Gr-1(+) and have long been known for their immunosuppressive function. We report that resveratrol effectively attenuated overall clinical scores as well as various pathological markers of colitis in IL-10(-/-) mice by down regulating Th1 responses. Resveratrol lessened the colitis-associated decrease in body weight and increased levels of serum amyloid A (SAA), CXCL10 and colon TNF-α, IL-6, RANTES, IL-12 and IL-1β concentrations. After resveratrol treatment, the percentage of CXCR3 expressing T cells was decreased in the spleen, mesenteric lymph nodes (MLN), and intestinal lamina propria (LP). However, the percentage and absolute numbers of CD11b(+) and Gr-1(+)cells in the lamina propria (LP) and spleen were increased after resveratrol treatment as compared with the vehicle treatment. Co-culture of resveratrol-induced CD11b(+) Gr-1(+) cells with T cells, attenuated T cell proliferation, and most importantly reduced IFN-γ and GM-CSF production by LP derived T cells from vehicle treated IL-10(-/-) mice with chronic colitis. The current study suggests that administration of resveratrol into IL-10(-/-) mice induces immunosuppressive CD11b(+) Gr-1(+) MDSCs in the colon, which correlates with reversal of established chronic colitis, and down regulation of mucosal and systemic CXCR3(+) expressing effector T cells as well as inflammatory cytokines in the colon. The induction of immunosuppressive CD11b(+) Gr-1(+) cells by resveratrol during colitis is unique, and suggests an as-yet-unidentified mode of anti-inflammatory action of this plant polyphenol.

Topics: Animals; CD11b Antigen; Cell Proliferation; Cell Separation; Chronic Disease; Colitis; Cytokines; Disease Progression; Enzyme-Linked Immunosorbent Assay; Feces; Flow Cytometry; Immunoglobulin A; Immunoglobulin G; Interleukin-10; Mice; Mice, Knockout; Mucous Membrane; Myeloid Cells; Receptors, Chemokine; Receptors, CXCR3; Resveratrol; Serum Amyloid A Protein; Spleen; Stilbenes; T-Lymphocytes; Weight Loss

The abnormalities associated with cancer cachexia include anorexia, weight loss, muscle loss and atrophy, anaemia and alterations in carbohydrate, lipid and protein metabolism. The aim of the present investigation was to examine the anti-wasting effects of some nutraceuticals such as genistein, resveratrol, epigallocatechin gallate and diallyl sulphide (DAS).. The in vitro effects of these nutraceuticals on proteolysis were examined in muscle cell cultures submitted to hyperthermia. The in vivo effects of DAS were also tested in cachectic tumour-bearing rats (Yoshida AH-130 ascites hepatoma).. Although all the nutraceuticals tested inhibited muscle proteolysis, the most promising effects were related with DAS. In vivo administration of DAS only leads to a small improvement in tibialis muscle and heart weights; however, administration of DAS to healthy animals increased all muscle weights, this being associated with a decreased gene expression of proteolytic systems components.. It may be suggested that DAS could be used to improve muscle mass during healthy conditions.

Topics: Allyl Compounds; Animals; Anorexia; Cachexia; Catechin; Cells, Cultured; Dietary Supplements; Genistein; Male; Muscle, Skeletal; Muscular Atrophy; Neoplasms; Rats; Rats, Wistar; Resveratrol; Stilbenes; Sulfides; Weight Loss

The mechanism by which cancer mediates muscle atrophy has been delineated in the past 3 decades and includes a prominent role of tumor-derived cytokines, such as IL-6, TNFα, and IL-1. These cytokines interact with their cognate receptors on muscle to activate the downstream transcription factor NF-κB and induce sarcomere proteolysis. Experimentally, inhibiting NF-κB signaling largely prevents cancer-induced muscle wasting, indicating its prominent role in muscle atrophy. Resveratrol, a natural phytoalexin found in the skin of grapes, has recently been shown to inhibit NF-κB in cancer cells, which led us to hypothesize that it might have a protective role in cancer cachexia. Therefore, we investigated whether daily oral resveratrol could protect against skeletal muscle loss and cardiac atrophy in an established mouse model. We demonstrate resveratrol inhibits skeletal muscle and cardiac atrophy induced by C26 adenocarcinoma tumors through its inhibition of NF-κB (p65) activity in skeletal muscle and heart. These studies demonstrate for the first time the utility of oral resveratrol therapy to provide clinical benefit in cancer-induced atrophy through the inhibition of NF-κB in muscle. These findings may have application in the treatment of diseases with parallel pathophysiologies such as muscular dystrophy and heart failure.

Topics: Adenocarcinoma; Administration, Oral; Animals; Body Composition; Cachexia; Cell Line, Tumor; Dose-Response Relationship, Drug; Echocardiography; Female; Gene Expression Regulation, Enzymologic; Heart; Mice; Muscle Proteins; Muscle, Skeletal; Muscular Atrophy; Myocardium; Neoplasm Transplantation; Random Allocation; Resveratrol; RNA, Messenger; Stilbenes; Transcription Factor RelA; Tripartite Motif Proteins; Ubiquitin-Protein Ligases; Weight Loss

Topics: Cachexia; Clinical Trials as Topic; Drug Approval; Drug Discovery; Drug Industry; Growth Hormone-Releasing Hormone; Humans; Pulmonary Disease, Chronic Obstructive; Pyrazoles; Receptors, Retinoic Acid; Research; Retinoic Acid Receptor gamma; Stilbenes; Weight Loss

Resveratrol, a natural polyphenolic compound that is found in grapes and red wine, increases metabolic rate, insulin sensitivity, mitochondrial biogenesis, and physical endurance and reduces fat accumulation in mice. Although it is thought that resveratrol targets Sirt1, this is controversial because resveratrol also activates 5' AMP-activated protein kinase (AMPK), which also regulates insulin sensitivity and mitochondrial biogenesis. Here, we use mice deficient in AMPKalpha1 or -alpha2 to determine whether the metabolic effects of resveratrol are mediated by AMPK.. Mice deficient in the catalytic subunit of AMPK (alpha1 or alpha2) and wild-type mice were fed a high-fat diet or high-fat diet supplemented with resveratrol for 13 weeks. Body weight was recorded biweekly and metabolic parameters were measured. We also used mouse embryonic fibroblasts deficient in AMPK to study the role of AMPK in resveratrol-mediated effects in vitro.. Resveratrol increased the metabolic rate and reduced fat mass in wild-type mice but not in AMPKalpha1(-/-) mice. In the absence of either AMPKalpha1 or -alpha2, resveratrol failed to increase insulin sensitivity, glucose tolerance, mitochondrial biogenesis, and physical endurance. Consistent with this, the expression of genes important for mitochondrial biogenesis was not induced by resveratrol in AMPK-deficient mice. In addition, resveratrol increased the NAD-to-NADH ratio in an AMPK-dependent manner, which may explain how resveratrol may activate Sirt1 indirectly.. We conclude that AMPK, which was thought to be an off-target hit of resveratrol, is the central target for the metabolic effects of resveratrol.

Topics: AMP-Activated Protein Kinases; Animals; Cells, Cultured; Drug Resistance; Enzyme Inhibitors; Fibroblasts; Glucose Intolerance; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Mitochondria; Muscle, Skeletal; NAD; Resveratrol; Sirtuin 1; Stilbenes; Weight Loss

Resveratrol, a phytoalexin found in grapes and red wines, has been reported to exhibit a wide range of pharmacological properties. In this study, we investigated the protective effect of resveratrol on hepatic injury induced by dimethylnitrosamine (DMN) in rats. Oral administration of resveratrol (20 mg/kg daily for 4 weeks) remarkably prevented the DMN-induced loss in body and liver weight, and inhibited the elevation of serum alanine transaminase, aspartate transaminase, alkaline phosphatase and bilirubin levels. Resveratrol also increased serum albumin and hepatic glutathione levels and reduced the hepatic level of malondialdehyde due to its antioxidant effect. Furthermore, DMN-induced elevation of hydroxyproline content was reduced in the resveratrol treated rats, the result of which was consistent with the reduction in type I collagen mRNA expression and the histological analysis of liver tissue stained with Sirius red. The reduction in hepatic stellate cell activation, as assessed by alpha-smooth muscle actin staining, and the reduction in transforming growth factor-beta1 mRNA expression were associated with resveratrol treatment. In conclusion, resveratrol exhibited in vivo hepatoprotective and antifibrogenic effects against DMN-induced liver injury, suggesting that resveratrol may be useful in the prevention of the development of hepatic fibrosis.

Topics: Alkylating Agents; Animals; Antioxidants; Biomarkers; Chemical and Drug Induced Liver Injury, Chronic; Dimethylnitrosamine; Down-Regulation; Hepatic Stellate Cells; Liver; Liver Cirrhosis; Male; Organ Size; Oxidative Stress; Protective Agents; Rats; Rats, Sprague-Dawley; Resveratrol; RNA, Messenger; Stilbenes; Transforming Growth Factor beta1; Weight Loss

Cyclosporine A (CsA) is a potent and effective immunosuppressive agent, but its use is frequently accompanied by severe renal toxicity. The causes for the nephrotoxicity of CsA have not been fully elucidated. Intrarenal vasoconstriction induced by several different mediators, both in humans and experimental animals have been proposed. The present study was designed to investigate the possible protective effect of resveratrol on CsA-induced nephrotoxicity and to explore the possible mechanism involved in resveratrol's effect. Eight groups of rats were employed in this study, group 1 served as control, group 2 rats were treated with olive oil (vehicle for CsA), group 3 rats were treated with CsA (20 mg/kg, s.c. for 21 days), groups 4, 5 and 6 received CsA along with resveratrol (2, 5 and 10 mg/kg, p.o. 24 h before and 21 days concurrently), respectively, group 7 rats were treated with NOS inhibitor, L-NAME (10 mg/kg) along with resveratrol and CsA and group 8 rats received L-NAME along with CsA. CsA administration for 21 days resulted in a marked renal oxidative stress, significantly deranged the renal functions, reduced the tissue and urine nitrite levels and markedly altered the renal morphology. Treatment with resveratrol (5 and 10 mg/kg) significantly improved the renal dysfunction; tissue and urine total nitric oxide levels, renal oxidative stress and prevented the alterations in renal morphology. Concurrent administration of L-NAME blocked the protective effect of resveratrol indicating that resveratrol exerts its protective effect by releasing nitric oxide. These results clearly demonstrate the pivotal role of nitric oxide in etiology of CsA nephrotoxicity and indicate the renoprotective potential of resveratrol in CsA nephrotoxicity.

Topics: Animals; Antioxidants; Blood Pressure; Blood Urea Nitrogen; Creatinine; Cyclosporine; Enzyme Inhibitors; Immunosuppressive Agents; Kidney; Lipid Peroxidation; Male; NG-Nitroarginine Methyl Ester; Nitrates; Nitric Oxide; Nitric Oxide Synthase; Nitrites; Phytoalexins; Plant Extracts; Rats; Rats, Wistar; Resveratrol; Sesquiterpenes; Stilbenes; Terpenes; Weight Loss

The potential for inhibitors of nuclear factor-kappaB (NF-kappaB) activation to act as inhibitors of muscle protein degradation in cancer cachexia has been evaluated both in vitro and in vivo. Activation of NF-kappaB is important in the induction of proteasome expression and protein degradation by the tumour factor, proteolysis-inducing factor (PIF), since the cell permeable NF-kappaB inhibitor SN50 (18 microM) attenuated the expression of 20S proteasome alpha-subunits, two subunits of the 19S regulator MSS1 and p42, and the ubiquitin-conjugating enzyme, E2(14k), as well as the decrease in myosin expression in murine myotubes. To assess the potential therapeutic benefit of NF-kappaB inhibitors on muscle atrophy in cancer cachexia, two potential inhibitors were employed; curcumin (50 microM) and resveratrol (30 microM). Both agents completely attenuated total protein degradation in murine myotubes at all concentrations of PIF, and attenuated the PIF-induced increase in expression of the ubiquitin-proteasome proteolytic pathway, as determined by the 'chymotrypsin-like' enzyme activity, proteasome subunits and E2(14k). However, curcumin (150 and 300 mg kg(-1)) was ineffective in preventing weight loss and muscle protein degradation in mice bearing the MAC16 tumour, whereas resveratrol (1 mg kg(-1)) significantly attenuated weight loss and protein degradation in skeletal muscle, and produced a significant reduction in NF-kappaB DNA-binding activity. The inactivity of curcumin was probably due to a low bioavailability. These results suggest that agents which inhibit nuclear translocation of NF-kappaB may prove useful for the treatment of muscle wasting in cancer cachexia.

Topics: Animals; Blood Proteins; Cachexia; Cells, Cultured; Chymotrypsin; Curcumin; Electrophoretic Mobility Shift Assay; Enzyme Activation; Enzyme Inhibitors; I-kappa B Proteins; Male; Mice; Mice, Inbred Strains; Muscle Fibers, Skeletal; Muscle, Skeletal; Neoplasms, Experimental; NF-kappa B; NF-KappaB Inhibitor alpha; Proteasome Endopeptidase Complex; Proteoglycans; Resveratrol; Stilbenes; Ubiquitins; Weight Loss