Diet-induced obesity is associated to an imbalance in the normal gut microbiota composition.Resveratrol and quercetin, widely known for their health beneficial properties, have low bioavailability and, when reach the colon, they are targets of the gut microbial ecosystem. Hence, the use of these molecules in obesity might be considered as a potential strategy to modulate intestinal bacterial composition. The purpose of this study was to determine whether trans-resveratrol and quercetin administration could counteract gut microbiota dysbiosis produced by high-fat sucrose diet (HFS) and in turn, improve gut health. Wistar rats were randomized into four groups fed a HFS diet supplemented or not with trans-resveratrol (15 mg/kg BW/day), quercetin (30 mg/kg BW/day) or a combination of both polyphenols at those doses. Administration of both polyphenols together prevented body-weight gain and reduced serum insulin levels. Moreover, individual supplementation of trans-resveratrol and quercetin effectively reduced serum insulin levels and insulin resistance.Quercetin supplementation generated a great impact on gut microbiota composition at different taxonomic levels, attenuating Firmicutes/Bacteroidetes ratio and inhibiting the growth of bacterial species previously associated to diet-induced obesity (Erysipelotrichaceae, Bacillus, Eubacterium 1 cylindroides). Overall, the administration of quercetin was found to be effective in lessening HFS dietinduced gut microbiota dysbiosis. In contrast, trans-resveratrol supplementation alone or in combination with quercetin, scarcely modified the profile of gut bacteria, but acted at intestinal level altering the mRNA expression of tight-junction proteins (TJPs) and inflammation associated genes.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common manifestations of chronic liver disease worldwide. The aim of the present study was to assess the effect of resveratrol on liver fat accumulation, as well as on the activity of those enzymes involved in lipogenesis and fatty acid oxidation in fa/fa Zucker rats. A total of thirty rats were assigned to three experimental groups and orally treated with resveratrol for 6 weeks, or without resveratrol (C: control group; RSV15 group: 15 mg/kg body weight per d; RSV45 group: 45 mg/kg body weight per d). Liver histological analysis was performed by microscopy. Levels of hepatic carnitine palmitoyltransferaseIa (CPT-Ia), acyl-coenzyme A oxidase (ACO), fatty acid synthase, glucose-6-phosphate dehydrogenase and malic enzyme were assessed by spectrophotometry, and acetyl-CoA carboxylase was assessed by radiometry. Commercial kits were used to determine serum TAG, NEFA, total HDL and non-HDL-cholesterol, glycerol, ketonic bodies, glucose, insulin, adiponectin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), hepatic TAG, thiobarbituric acid reactive substrates, GSH (GSSG) and superoxide dismutase. Resveratrol reduced liver weight and TAG content. It did not modify the activity of lipogenic enzymes but it did increase CPT-Ia and ACO activities. NEFA and ALP were reduced in both resveratrol-treated groups. AST/GOT was reduced only by the lowest dose. ALT/GPT, TAG and adiponectin remained unchanged. Resveratrol reduced liver oxidative stress. This study demonstrates that resveratrol can protect the liver from NAFLD by reducing fatty acid availability. Moreover, resveratrol also protects liver from oxidative stress.

BackgroundA remarkable range of biological functions have been ascribed to resveratrol. Recently, this polyphenol has been shown to have body fat lowering effects. The aim of the present study was to assess some of the potential underlying mechanisms of action which take place in adipose tissue.MethodsSixteen male Sprague-Dawley rats were randomly divided into two groups: control and treated with 30 mg resveratrol/kg body weight/d. All rats were fed an obesogenic diet and after six weeks of treatment white adipose tissues were dissected. Lipoprotein lipase activity was assessed by fluorimetry, acetyl-CoA carboxylase by radiometry, and malic enzyme, glucose-6P-dehydrogenase and fatty acid synthase by spectrophotometry. Gene expression levels of acetyl-CoA carboxylase, fatty acid synthase, lipoprotein lipase, hormone-sensitive lipase, adipose triglyceride lipase, PPAR-gamma, SREBP-1c and perilipin were assessed by Real time RT-PCR. The amount of resveratrol metabolites in adipose tissue was measured by chromatography.ResultsThere was no difference in the final body weight of the rats; however, adipose tissues were significantly decreased in the resveratrol-treated group. Resveratrol reduced the activity of lipogenic enzymes, as well as that of heparin-releasable lipoprotein lipase. Moreover, a significant reduction was induced by this polyphenol in hormone-sensitive lipase mRNA levels. No significant changes were observed in other genes. Total amount of resveratrol metabolites in adipose tissue was 2.66 ± 0.55 nmol/g tissue.ConclusionsIt can be proposed that the body fat-lowering effect of resveratrol is mediated, at least in part, by a reduction in fatty acid uptake from circulating triacylglycerols and also in de novo lipogenesis.