MicroRNA-206 prevents hepatosteatosis and hyperglycemia by facilitating insulin signaling and impairing lipogenesis.
MicroRNA-206 prevents hepatosteatosis and hyperglycemia by facilitating insulin signaling and impairing lipogenesis.
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MicroRNA-206通过促进胰岛素信号传导和损害脂肪生成来防止肝造成病和高血糖。
DOI：
10.1016/j.jhep.2016.12.016
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发表时间：
2017-04
影响因子：
25.7
通讯作者：
Song G
中科院分区：
文献类型：
--
作者：
Wu H;Zhang T;Pan F;Steer CJ;Li Z;Chen X;Song G
The paradox of selective hepatic insulin resistance, wherein the insulin-resistant liver fails to suppress glucose production but continues to produce lipids, has been central to the pathophysiology of hepatosteatosis and hyperglycemia. Our study was designed to investigate the mechanism(s) by which microRNA-206 alleviates the pathogenesis of hepatosteatosis and hyperglycemia. Dietary obese mice induced by a high fat diet were used to study the role of microRNA-206 in the pathogenesis of hepatosteatosis and hyperglycemia. A mini-circle vector was used to deliver microRNA-206 into the livers of mice. Lipid accumulation impaired biogenesis of microRNA-206 in fatty livers of dietary obese mice and human hepatocytes (p <0.01). Delivery of microRNA-206 into the livers of dietary obese mice resulted in the strong therapeutic effects on hepatosteatosis and hyperglycemia. Mechanistically, miR-206 interacted with the 3′ untranslated region of PTPN1 (protein tyrosine phosphatase, non-receptor type 1) and induced its degradation. By inhibiting PTPN1 expression, microRNA-206 facilitated insulin signaling by promoting phosphorylation of INSR (insulin receptor) and impaired hepatic lipogenesis by inhibiting Srebp1c transcription. By simultaneously modulating lipogenesis and insulin signaling, microRNA-206 reduced lipid (p = 0.006) and glucose (p = 0.018) production in human hepatocytes and livers of dietary obese mice (p <0.001 and p <0.01 respectively). Re-introduction of Ptpn1 into livers offset the inhibitory effects of microRNA-206, indicating that PTPN1 mediates the inhibitory effects of microRNA-206 on both hepatosteatosis and hyperglycemia. MicroRNA-206 is a potent inhibitor of lipid and glucose production by simultaneously facilitating insulin signaling and impairing hepatic lipogenesis. Our findings potentially provide a novel therapeutic agent for both hepatosteatosis and hyperglycemia.
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影响因子：
7.7
作者：
Delibegovic M;Zimmer D;Kauffman C;Rak K;Hong EG;Cho YR;Kim JK;Kahn BB;Neel BG;Bence KK
通讯作者：
Bence KK
影响因子：
7.7
作者：
González-Rodríguez A;Mas Gutierrez JA;Sanz-González S;Ros M;Burks DJ;Valverde AM
通讯作者：
Valverde AM
DOI：
10.1083/jcb.200603008
发表时间：
2006-08-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kim HK;Lee YS;Sivaprasad U;Malhotra A;Dutta A
通讯作者：
Dutta A
影响因子：
--
作者：
Tao J;Ji J;Li X;Ding N;Wu H;Liu Y;Wang XW;Calvisi DF;Song G;Chen X
通讯作者：
Chen X
影响因子：
4.8
作者：
Huang, Jiansheng;Jia, Yuzhi;Reddy, Janardan K.
通讯作者：
Reddy, Janardan K.