title: ROCK1 reduces mitochondrial content and irisin production in muscle suppressing adipocyte browning and impairing insulin sensitivity.
abstract: 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.
authors.affiliation: Nephrology Division, Shanxi Province People's Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Xiaoshuang
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Nephrology Division, Shanxi Province People's Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Rongshan
authors.initials: R
authors.lastname: Li
authors.affiliation: Nephrology Division, Second Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Xinyan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Nephrology Division, Second Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Wang
authors.affiliation: Nephrology Division, The third affiliated hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Hui
authors.affiliation: Endocrinology Division, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Chan
authors.affiliation: Endocrinology Division, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Pradip K
authors.initials: PK
authors.lastname: Saha
authors.affiliation: Nephrology Division, Department of Medicine, Selzman Institute for Kidney Health, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Zhaoyong
authors.initials: Z
authors.lastname: Hu
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D004734:Energy Metabolism / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D022722:Thermogenesis / Q000502:physiology; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: C571428:FNDC5 protein, mouse; D005353:Fibronectins; D024101:Mitochondrial Proteins; C515854:Rock1 protein, mouse; D054460:rho-Associated Kinases; D005947:Glucose