Recent studies have investigated the anti-obesity effect of resveratrol, but the pathways through which resveratrol resists obesity are not clear. In the present study, we hypothesize that resveratrol exerts anti-obesity effects that are likely mediated by mechanisms of regulating gut microbes, and in turn, improving fat storage and metabolism. Gut microbes, glucose and lipid metabolism in high-fat diet (HF) mice in vivo are investigated after resveratrol treatment. Several biochemical markers are measured. Fluorescence in situ hybridization and flow cytometry are used to monitor and quantify the changes in gut microbiota. The key genes related to fat storage and metabolism in the liver and visceral adipose tissues are measured by real-time PCR. The results show that resveratrol (200 mg per kg per day) significantly lowers both body and visceral adipose weights, and reduces blood glucose and lipid levels in HF mice. Resveratrol improves the gut microbiota dysbiosis induced by the HF diet, including increasing the Bacteroidetes-to-Firmicutes ratios, significantly inhibiting the growth of Enterococcus faecalis, and increasing the growth of Lactobacillus and Bifidobacterium. Furthermore, resveratrol significantly increases the fasting-induced adipose factor (Fiaf, a key gene negatively regulated by intestinal microbes) expression in the intestine. Resveratrol significantly decreases mRNA expression of Lpl, Scd1, Ppar-γ, Acc1, and Fas related to fatty acids synthesis, adipogenesis and lipogenesis, which may be driven by increased Fiaf expression. The Pearson's correlation coefficient shows that there is a negative correlation between the body weight and the ratios of Bacteroidetes-to-Firmicutes. Therefore, resveratrol mediates the composition of gut microbes, and in turn, through the Fiaf signaling pathway, accelerates the development of obesity.

The aim of this study was to examine whether malondialdehyde (MDA) formation, a marker of oxidant stress, is altered in different stages of development of hyperlipidemia and whether it correlates with atherogenic index (AI), an important risk factor of atherosclerosis. Commercial kits were used to measure the levels of lipid profile and antioxidant status in the serum of 15 hyperlipidemic patients and 30 age and sex-matched normolipidemic subjects. The normolipidemic subjects were divided into lower and higher lipid groups according to their blood lipid level. The activities of superoxide dismutase and glutathione peroxidase decreased in higher lipid group compared with lower lipid group, and were even lower in hyperlipidemic subjects. An increase in the levels of MDA, triglycerides, total cholesterol and LDL-C concentration were observed in higher lipid group, and even significantly increased in hyperlipidemic patients. A significant progressive decline in HDL-C concentration was found during hyperlipidemia evolution. There was a positive correlation between MDA and AI (r = 0.61, p<0.05). These data indicate that oxidative stress is an early event in the evolution of hyperlipidemia, and appropriate support for enhancing antioxidant supply in higher lipid subjects may help prevent the course of the disease.

Methionine-restricted diets (MRD) have been shown to prevent high fat diet (HFD) induced complications including fat accumulation, insulin sensitivity decrease, oxidative stress and inflammation increase. We hypothesized that intestinal microbiota changes may mediate these effects, and this study aims to prove this hypothesis. Mice were fed a normal diet (ND, 0.86% methionine + 4% fat), a HF diet (HFD, 0.86% methionine + 20% fat), or a MRD (0.17% methionine + 20% fat) and euthanized at week 22. Our results showed that the HFD induced fat accumulation and gut microbiota dysbiosis; reduced short-chain fatty acid (SCFA) production; and increased intestinal permeability, inflammatory response, and oxidative stress. The MRD decreased the body weight, body fat rate, and blood glucose and plasma lipid levels; increased the abundance of putative SCFA-producing bacteria Bifidobacterium, Lactobacillus, Bacteroides, Roseburia, Coprococcus, and Ruminococcus and inflammation-inhibiting bacteria Oscillospira and Corynebacterium; and decreased the abundance of inflammation-producing bacteria Desulfovibrio in colonic contents. Moreover, the MRD improved intestinal barrier function, inflammatory response, and oxidative stress, and altered the metabolite levels of colonic contents (such as increasing SCFA and bile acid concentrations); the latter may have contributed to the prevention of HFD-induced obesity. In conclusion, the MRD can improve gut health by regulating the intestinal microbiota and its metabolite profiles in the HFD mice. Reducing methionine intake by simple dietary adjustment may be an effective method to improve intestinal health in animals and humans.