Differential effects of low-dose resveratrol on adiposity and hepatic steatosis in diet-induced obese mice

Consumption of a high-fat diet (HFD) enriched in saturated fat induces excessive weight gain due to adiposity, which can lead to metabolic complications, as well as increased risk of fatty liver disease and CVD. The present study investigated the underlying mechanism and dose-response effects of resveratrol (RV) on obesity, hepatic steatosis and dyslipidaemia in mice fed a HFD. Male C57BL/6J mice were fed a normal diet or a HFD (20% fat, w/w) combined with 0.005 or 0.02% (w/w) RV for 10 weeks. As expected, mice fed a HFD developed obesity, as shown by increased body weight gain, visceral fat, hepatic fat and plasma cholesterol. RV significantly reduced visceral fat and plasma NEFA. In the liver of HFD-fed mice, RV significantly reduced TAG and cholesterol, as well as lipid droplet number and size. A low dose of RV (0.005 %) appeared to be more effective than a higher dose of RV (0.02 %) for suppressing adiposity and hepatic steatosis development with a significant decrease in body weight gain, plasma TAG and total cholesterol levels. These changes were seemingly attributable to a suppression of the fatty acid (FA) synthase, glucose-6-phosphate dehydrogenase, and phosphatidate phosphohydrolase and/or an activation of FA oxidation in the liver and epididymal adipose tissue. In conclusion, daily consumption of a low dose of RV is effective for protecting against diet-induced obesity, hepatic steatosis and dyslipidaemia in HFD-fed mice.