Resveratrol Improves Insulin Resistance Hyperglycemia and Hepatosteatosis But Not Hypertriglyceridemia, Inflammation, and Life Span in a Mouse Model for Werner Syndrome
Resveratrol Improves Insulin Resistance Hyperglycemia and Hepatosteatosis But Not Hypertriglyceridemia, Inflammation, and Life Span in a Mouse Model for Werner Syndrome
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DOI：
10.1093/gerona/glq184
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发表时间：
2011-03-01
影响因子：
5.1
通讯作者：
Lebel, Michel
中科院分区：
文献类型：
--
作者：
Labbe, Adam;Garand, Chantal;Lebel, Michel
沃纳综合征是一种由RecQ样DNA解旋酶突变引起的过早衰老疾病。缺乏WRN同源物的解旋酶结构域的小鼠表现出沃纳综合征的许多特征，包括促氧化状态和较短的平均寿命。在这里，我们表明，白藜芦醇补充改善高血糖症和胰岛素抵抗表型在这些Writ突变小鼠。此外，白藜芦醇逆转肝脏脂肪变性，脂质过氧化反应，并在这些小鼠中观察到的出窗表型。然而，白藜芦醇并没有改善高脂血症，炎症应激，也没有延长这些突变小鼠的平均寿命。对肝组织的微阵列和生物途径富集分析显示，白藜芦醇主要降低Writ突变小鼠的胰岛素生成，并增加参与胰岛素信号通路和谷胱甘肽代谢的基因。最后，白藜芦醇治疗的突变小鼠表现出淋巴瘤和几个实体瘤的频率增加。这些结果表明，白藜芦醇补充剂可能至少对沃纳综合征患者的代谢有益。
Werner syndrome is a premature aging disorder caused by mutations in a RecQ-like DNA helicase. Mice lacking the helicase domain of the WRN homologue exhibit many features of Werner syndrome, including a pro-oxidant status and a shorter mean life span. Here, we show that resveratrol supplementation improved the hyperglycemia and the insulin resistance phenotype in these Writ mutant mice. In addition, resveratrol reversed liver steatosis, lipid peroxidaton, and the defenestration phenotypes observed in such mice. Resveratrol, however, did not improve the hypertriglyceridemia, inflammatory stress, nor extend the mean life span of these mutant mice. Microarray and biologic pathway enrichment analyses on liver tissues revealed that resveratrol mainly decreased lipidogenesis and increased genes involved in the insulin signaling pathway and the glutathione metabolism in Writ mutant mice. Finally, resveratrol-treated mutant mice exhibited an increase in the frequency of lymphoma and of several solid tumors. These results indicate that resveratrol supplementation might exert at least metabolic benefits for Werner syndrome patients.