Loss-of-function myostatin mutation increases insulin sensitivity and browning of white fat in Meishan pigs
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Chunbo Cai1,2, Lili Qian1,2, Shengwang Jiang1, Youde Sun4, Qingqing Wang1, Dezun Ma1, Gaojun Xiao1, Biao Li1, Shanshan Xie1, Ting Gao1,3, Yaoxing Chen3, Jie Liu5, Xiaorong An2, Wentao Cui1, Kui Li1
1Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, P. R. China
2State Key Laboratory of Agro Biotechnology, China Agricultural University, Beijing, 100193, P. R. China
3College of Animal Medicine, China Agricultural University, Beijing, 100193, P. R. China
4Institute of Animal Sciences, Qingdao, 266100, P. R. China
5Department of Bioengineering and Biotechnology, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, 266042, P. R. China
Wentao Cui, email: email@example.com
Kui Li, email: firstname.lastname@example.org
Keywords: myostatin deficiency, skeletal muscle, fat, insulin sensitivity, irisin
Received: December 01, 2016 Accepted: March 22, 2017 Published: April 04, 2017
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.
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