Resveratrol attenuates excessive ethanol exposure induced insulin resistance in rats via improving NAD+/NADH ratio

Scope: Resveratrol has been shown to improve insulin resistance via activating the NAD(+)-dependent deacetylase SIRT1, but the effects of resveratrol on ethanol-induced insulin resistance remain unclear. This study was designed to explore the potential mechanism by which resveratrol ameliorated ethanol-induced insulin resistance, focusing on its regulations on the ratio of NAD(+)/NADH and SIRT1 expression. Methods and results: Male Sprague-Dawley rats were fed either control or ethanol liquid diets containing 0.8, 1.6 and 2.4g/kg.bw ethanol with or without 100 mg/kg.bw resveratrol for 22 weeks. Resveratrol improved ethanol (2.4 g/kg.bw) induced reductions in insulin sensitivity, SIRT1 expression (51%, P < 0.05), NAD(+)/NADH ratio (196%, P < 0.01) as well as the expression and activity of ALDH2 while decreased the augmentations in the expression and activity of ADH and CYP2E1. In primary rat hepatocytes, ethanol exposure (25 mmol/L, 24 h) similarly decreased SIRT1 expression and NAD(+)/NADH ratio (33%, P < 0.05; 32%, P < 0.01), and 0.1 mol/L resveratrol treatment reversed these decreases and inhibited the expressions of ADH and CYP2E1. Conclusion: Resveratrol exhibits benefits against ethanol-induced insulin resistance via improving the ratio of NAD(+)/NADH to regulate SIRT1, which is associated with the modulation of ethanol metabolism enzymes.