sirtuin 6脂肪通过产生IL-4促使巨噬细胞向M2极化，并维持小鼠和人类的全身胰岛素敏感性。,Experimental & Molecular Medicine

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sirtuin 6脂肪通过产生IL-4促使巨噬细胞向M2极化，并维持小鼠和人类的全身胰岛素敏感性。
Experimental & Molecular Medicine ( IF 9.5 ) Pub Date : 2019-05-21 , DOI: 10.1038/s12276-019-0256-9
Mi-Young Song ₁ , Sang Hoon Kim ₂ , Ga-Hee Ryoo ₁ , Mi-Kyung Kim ₃ , Hye-Na Cha ₄ , So-Young Park ₄ , Hong Pil Hwang ₂ , Hee Chul Yu ₂ , Eun Ju Bae ₅ , Byung-Hyun Park ₁

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脂肪组织炎症是肥胖和与肥胖相关的胰岛素抵抗的可再现特征。尽管sirtuin 6（Sirt6）缺乏症以前曾与饮食引起的肥胖和全身性胰岛素抵抗有关，但Sirt6在调节正常食物和人体内的小鼠脂肪组织炎症和全身代谢功能障碍中的脂肪细胞特异性作用仍然难以捉摸。在这里，我们使用Adipoq-Cre介导的脂肪细胞特异性Sirt6基因敲除（aS6KO）小鼠，探讨了脂肪细胞Sirt6是否抑制脂肪组织炎症及其潜在机制。饲喂正常食物的aS6KO小鼠比野生型小鼠具有更多的体重和脂肪量，并表现出葡萄糖耐量和全身性胰岛素抵抗。血浆和组织细胞因子的测量以及脂肪基质血管细胞的流式细胞仪分析表明，aS6KO小鼠脂肪组织中交替激活的M2巨噬细胞减少。机械上，Sirt6以细胞自主方式调节脂肪细胞对典型2型细胞因子IL-4的表达，进而影响M2巨噬细胞的极化。与动物实验数据一致，由体重指数，空腹血糖和HbA1c证明的肥胖和胰岛素抵抗程度与人内脏脂肪组织中Sirt6的表达呈负相关。总的来说，这些结果表明脂肪细胞Sirt6可以独立于饮食来调节体重增加和胰岛素敏感性，

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Adipose sirtuin 6 drives macrophage polarization toward M2 through IL-4 production and maintains systemic insulin sensitivity in mice and humans.

Adipose tissue inflammation is a reproducible feature of obesity and obesity-linked insulin resistance. Although sirtuin 6 (Sirt6) deficiency has previously been implicated in diet-induced obesity and systemic insulin resistance, the adipocyte-specific role of Sirt6 in the regulation of adipose tissue inflammation and systemic metabolic dysfunction in mice fed normal chow and in humans remains elusive. Here, using Adipoq-Cre-mediated adipocyte-specific Sirt6 knockout (aS6KO) mice, we explored whether adipocyte Sirt6 inhibits adipose tissue inflammation and its underlying mechanism. aS6KO mice fed normal chow gained more body weight and fat mass than wild-type mice and exhibited glucose intolerance and systemic insulin resistance. Measurement of plasma and tissue cytokines and flow cytometric analysis of adipose stromal vascular cells indicated a decrease in alternatively activated M2 macrophages in the adipose tissue of aS6KO mice. Mechanistically, Sirt6 regulated the expression of the canonical type 2 cytokine IL-4 by adipocytes in a cell autonomous manner, which in turn affects M2 macrophage polarization. Consistent with animal experimental data, the degree of obesity and insulin resistance demonstrated by the body mass index, fasting blood glucose and HbA1c correlated negatively with the expression of Sirt6 in human visceral fat tissues. Collectively, these results suggest that adipocyte Sirt6 regulates body weight gain and insulin sensitivity independent of diet, and the increased IL-4 production by Sirt6 and resultant M2 polarization of adipose tissue macrophages may attenuate proinflammatory responses in adipose tissue.

更新日期：2019-05-21

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