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Sci Rep. 2016 Jul 14;6:29669. doi: 10.1038/srep29669.

ROCK1 reduces mitochondrial content and irisin production in muscle suppressing adipocyte browning and impairing insulin sensitivity.

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Nephrology Division, Shanxi Province People's Hospital of Shanxi Medical University, Taiyuan, China.
Nephrology Division, Second Hospital of Shanxi Medical University, Taiyuan, China.
Nephrology Division, The third affiliated hospital of Sun Yat-sen University, Guangzhou, China.
Endocrinology Division, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
Nephrology Division, Department of Medicine, Selzman Institute for Kidney Health, Baylor College of Medicine, Houston, Texas, USA.


Irisin reportedly promotes the conversion of preadipocytes into "brown-like" adipocytes within subcutaneous white adipose tissue (WAT) via a mechanism that stimulates UCP-1 expression. An increase in plasma irisin has been associated with improved obesity and insulin resistance in mice with type 2 diabetes. But whether a low level of irisin stimulates the development of obesity has not been determined. In studying mice with muscle-specific constitutive ROCK1 activation (mCaROCK1), we found that irisin production was down-regulated and the mice developed obesity and insulin resistance. Therefore, we studied the effects of irisin deficiency on energy metabolism in mCaROCK1 mice. Constitutively activation of ROCK1 in muscle suppressed irisin expression in muscle resulting in a low level of irisin in circulation. Irisin deficiency reduced heat production and decreased the expression of uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) and subcutaneous WAT. Moreover, mCaROCK1 mice also displayed impaired glucose tolerance. Notably, irisin replenishment in mCaROCK1 mice partially reversed insulin resistance and obesity and these changes were associated with increased expression of UCP1 and Pref-1 in subcutaneous WAT. These results demonstrate that irisin mediates muscle-adipose tissue communication and regulates energy and glucose homeostasis. Irisin administration can correct obesity and insulin resistance in mice.

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