miR-30a Remodels Subcutaneous Adipose Tissue Inflammation to Improve Insulin Sensitivity in Obesity.
miR-30a Remodels Subcutaneous Adipose Tissue Inflammation to Improve Insulin Sensitivity in Obesity.
复制标题
miR-30a 重塑皮下脂肪组织炎症，改善肥胖患者的胰岛素敏感性
作者：
Koh EH;Chernis N;Saha PK;Xiao L;Bader DA;Zhu B;Rajapakshe K;Hamilton MP;Liu X;Perera D;Chen X;York B;Trauner M;Coarfa C;Bajaj M;Moore DD;Deng T;McGuire SE;Hartig SM
慢性炎症伴随肥胖并限制皮下白色脂肪组织（WAT）的可扩张性，加速胰岛素抵抗和2型糖尿病的发展。MicroRNA（miRNAs）影响脂肪细胞中许多代谢基因的表达，但WAT中的生理作用仍不清楚。在这里，我们报告了皮下WAT中的miRNA miR-30 a的表达与肥胖小鼠和人类的胰岛素敏感性相对应。为了检验WAT中miR-30 a表达的恢复改善胰岛素敏感性的假设，我们将表达miR-30 a的腺病毒（Adv）注射到糖尿病小鼠的皮下脂肪垫中。肥胖小鼠皮下WAT贮库中的外源性miR-30 a表达与胰岛素敏感性改善和能量消耗增加以及肝脏异位脂肪沉积减少和WAT炎症减少相结合。高通量蛋白质组分析和RNA-Seq表明，miR-30 a靶向转录因子STAT 1，以限制促炎细胞因子干扰素-γ（IFN-γ）的作用，否则会限制WAT扩增并降低胰岛素敏感性。我们进一步证明了miR-30 a对抗IFN-γ的作用，这表明miR-30 a在保护脂肪细胞对抗降低外周胰岛素敏感性的促炎细胞因子方面具有重要作用。总之，我们的数据确定了一个关键的分子信号传导轴，其中的元素参与解耦肥胖代谢功能障碍。
Chronic inflammation accompanies obesity and limits subcutaneous white adipose tissue (WAT) expandability, accelerating the development of insulin resistance and type 2 diabetes mellitus. MicroRNAs (miRNAs) influence expression of many metabolic genes in fat cells, but physiological roles in WAT remain poorly characterized. Here, we report that expression of the miRNA miR-30a in subcutaneous WAT corresponds with insulin sensitivity in obese mice and humans. To examine the hypothesis that restoration of miR-30a expression in WAT improves insulin sensitivity, we injected adenovirus (Adv) expressing miR-30a into the subcutaneous fat pad of diabetic mice. Exogenous miR-30a expression in the subcutaneous WAT depot of obese mice coupled improved insulin sensitivity and increased energy expenditure with decreased ectopic fat deposition in the liver and reduced WAT inflammation. High-throughput proteomic profiling and RNA-Seq suggested that miR-30a targets the transcription factor STAT1 to limit the actions of the proinflammatory cytokine interferon-γ (IFN-γ) that would otherwise restrict WAT expansion and decrease insulin sensitivity. We further demonstrated that miR-30a opposes the actions of IFN-γ, suggesting an important role for miR-30a in defending adipocytes against proinflammatory cytokines that reduce peripheral insulin sensitivity. Together, our data identify a critical molecular signaling axis, elements of which are involved in uncoupling obesity from metabolic dysfunction.
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影响因子：
3.7
作者：
Corcoran DL;Pandit KV;Gordon B;Bhattacharjee A;Kaminski N;Benos PV
通讯作者：
Benos PV
影响因子：
30.5
作者：
Chung KJ;Chatzigeorgiou A;Economopoulou M;Garcia-Martin R;Alexaki VI;Mitroulis I;Nati M;Gebler J;Ziemssen T;Goelz SE;Phieler J;Lim JH;Karalis KP;Papayannopoulou T;Blüher M;Hajishengallis G;Chavakis T
通讯作者：
Chavakis T
影响因子：
29
作者：
Altshuler-Keylin S;Shinoda K;Hasegawa Y;Ikeda K;Hong H;Kang Q;Yang Y;Perera RM;Debnath J;Kajimura S
通讯作者：
Kajimura S
影响因子：
21.3
作者：
通讯作者：
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影响因子：
16.6
作者：
Hamilton MP;Rajapakshe K;Hartig SM;Reva B;McLellan MD;Kandoth C;Ding L;Zack TI;Gunaratne PH;Wheeler DA;Coarfa C;McGuire SE
通讯作者：
McGuire SE