Loss-of-function myostatin mutation increases insulin sensitivity and browning of white fat in Meishan pigs

// Chunbo Cai 1, 2 , Lili Qian 1, 2 , Shengwang Jiang 1 , Youde Sun 4 , Qingqing Wang 1 , Dezun Ma 1 , Gaojun Xiao 1 , Biao Li 1 , Shanshan Xie 1 , Ting Gao 1, 3 , Yaoxing Chen 3 , Jie Liu 5 , Xiaorong An 2 , Wentao Cui 1 , Kui Li 1 1 Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, P. R. China 2 State Key Laboratory of Agro Biotechnology, China Agricultural University, Beijing, 100193, P. R. China 3 College of Animal Medicine, China Agricultural University, Beijing, 100193, P. R. China 4 Institute of Animal Sciences, Qingdao, 266100, P. R. China 5 Department of Bioengineering and Biotechnology, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, 266042, P. R. China Correspondence to: Wentao Cui, email: cuiwentao@caas.cn Kui Li, email: likui@caas.cn Keywords: myostatin deficiency, skeletal muscle, fat, insulin sensitivity, irisin Received: December 01, 2016      Accepted: March 22, 2017      Published: April 04, 2017 ABSTRACT Myostatin-deficient mice showed a remarkable hypertrophy of skeletal muscle, with a decreased fat mass and enhanced insulin sensitivity. Currently, it is unclear if the inhibition of myostatin could be used as an approach to treat human obesity and insulin resistance. In this study, we investigated if the inhibition of porcine myostatin has any effect on fat deposition and insulin sensitivity using genetically engineered Meishan pigs containing a myostatin loss-of-function mutation ( Mstn −/− ). Our results indicated that, when compared with wild-type pigs, the amount of subcutaneous fat and leaf fat of Mstn –/– pigs were significantly decreased mainly due to the browning of subcutaneous adipose tissue. Additionally, the serum insulin level decreased and the insulin sensitivity increased significantly in Mstn –/– pigs. Moreover, we found a significant increase in levels of insulin receptor and insulin receptor substrate proteins in skeletal muscle of Mstn –/– pigs, which then activating the insulin signaling pathway. Irisin-mediated regulation is not the only pathway for the activation of insulin signal in Mstn −/− skeletal muscle. This study provides valuable insight for the treatment of human obesity and diabetes mellitus.