骨骼肌分泌的肌动蛋白白细胞介素-6可诱导肌肉生长抑制素基因敲除猪的白色脂肪组织转化为米色脂肪组织。

Skeletal muscle-secreted myokine interleukin-6 induces white adipose tissue conversion into beige adipose tissue in myostatin gene knockout pigs.

作者信息

Xuan M-F, Luo Z-B, Han S-Z, Li Z-Y, Gao K, Liu X-Y, Chang S-Y, Jin Z-Y, Choe H-M, Paek H-J, Quan B-H, Yin X-J, Kang J-D

机构信息

Department of Animal Science, Agricultural College, Yanbian University, Yanji, Jilin, 133002, China.

Department of Animal Science, Agricultural College, Yanbian University, Yanji, Jilin, 133002, China; Jilin Provincial Key Laboratory of Transgenic Animal and Embryo Engineering, Yanbian University, Yanji, Jilin, 133002, China.

出版信息

Domest Anim Endocrinol. 2022 Jan;78:106679. doi: 10.1016/j.domaniend.2021.106679. Epub 2021 Sep 7.

DOI:10.1016/j.domaniend.2021.106679

PMID:34715416

Abstract

Myostatin (MSTN) is primarily expressed in skeletal muscle and plays an important role in the regulation of muscle growth and development as well as fat deposition; however, little is known about the molecular mechanism through which MSTN regulates body fat deposition. Therefore, in this study, we sought to identify the signaling pathways through which MSTN regulates fat accumulation in pigs. MSTN knockout (MSTN) pigs showed increased muscle mass, decreased fat mass, and a leaner body composition. In this study, we found that the adipose tissue of MSTN pigs exhibits the characteristics of beige adipose tissue, and the mRNA expression levels of beige adipose marker genes, including UCP3, Cidea, and CD137, were significantly increased. Remarkably, the observed beige phenotype was not adipocyte autonomous but rather caused by muscle-secreted myokine interleukin (IL)-6. This occurrence results in increased AMP-activated protein kinase (AMPK) phosphorylation in adipose tissue, which subsequently activates peroxisome proliferator-activated receptor gamma coactivator 1α and the conversion of white adipocytes to beige in pigs. Therefore, we concluded that MSTN deficiency leads to increased IL-6 secretion in skeletal muscle and activates AMPK in adipocytes, thereby increasing the beige adipose tissue in MSTN pigs.

摘要

肌肉生长抑制素（MSTN）主要在骨骼肌中表达，在肌肉生长发育以及脂肪沉积的调节中发挥重要作用；然而，关于MSTN调节体脂沉积的分子机制知之甚少。因此，在本研究中，我们试图确定MSTN调节猪脂肪积累的信号通路。肌肉生长抑制素基因敲除（MSTN）猪表现出肌肉量增加、脂肪量减少和更瘦的身体组成。在本研究中，我们发现MSTN猪的脂肪组织呈现出米色脂肪组织的特征，包括解偶联蛋白3（UCP3）、细胞死亡诱导DFFA样效应因子A（Cidea）和CD137在内的米色脂肪标记基因的mRNA表达水平显著增加。值得注意的是，观察到的米色表型并非脂肪细胞自主性的，而是由肌肉分泌的肌动蛋白白细胞介素（IL）-6引起的。这种情况导致脂肪组织中AMP活化蛋白激酶（AMPK）磷酸化增加，随后激活过氧化物酶体增殖物激活受体γ共激活因子1α，并使猪的白色脂肪细胞转变为米色脂肪细胞。因此，我们得出结论，MSTN缺乏导致骨骼肌中IL-6分泌增加，并激活脂肪细胞中的AMPK，从而增加MSTN猪的米色脂肪组织。