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

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Abstract
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 2.4 g/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 μmol/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.
Funding Information
  • National Natural Science Foundation of China (81172657, 81573149)

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