Resveratrol attenuates excessive ethanol exposure induced insulin resistance in rats via improving NAD+/NADH ratio
Resveratrol attenuates excessive ethanol exposure induced insulin resistance in rats via improving NAD+/NADH ratio
复制标题
白藜芦醇通过改善 NAD/NADH 比率来减轻过量乙醇暴露引起的大鼠胰岛素抵抗
DOI：
10.1002/mnfr.201700087
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发表时间：
2017-11-01
影响因子：
5.2
通讯作者：
Hao, Liping
中科院分区：
文献类型：
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作者：
Luo, Gang;Huang, Bingqing;Hao, Liping
范围：白藜芦醇已被证明可以通过激活 NAD(+) 依赖性脱乙酰酶 SIRT1 来改善胰岛素抵抗，但白藜芦醇对乙醇诱导的胰岛素抵抗的影响仍不清楚。本研究旨在探讨白藜芦醇改善乙醇诱导的胰岛素抵抗的潜在机制，重点关注其对NAD(+)/NADH比值和SIRT1表达的调节。方法和结果：雄性Sprague-Dawley大鼠饲喂对照或含0.8、1.6和2.4g/kg.bw乙醇的乙醇流质饲料，添加或不添加100 mg/kg.bw白藜芦醇22周。白藜芦醇改善乙醇 (2.4 g/kg.bw) 诱导的胰岛素敏感性、SIRT1 表达 (51%, P < 0.05)、NAD(+)/NADH 比值 (196%, P < 0.01) 以及 ALDH2 表达和活性的降低，同时降低 ADH 和 CYP2E1 表达和活性的增强。在原代大鼠肝细胞中，乙醇暴露（25 mmol/L，24 h）同样降低了 SIRT1 表达和 NAD(+)/NADH 比值（33%，P < 0.05；32%，P < 0.01），0.1 mol/L 白藜芦醇治疗逆转了这些降低并抑制了 ADH 和 CYP2E1 的表达。结论：白藜芦醇通过以下方式对抗乙醇诱导的胰岛素抵抗：提高NAD(+)/NADH的比例来调节SIRT1，SIRT1与乙醇代谢酶的调节有关。
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.