Abstract：
Recently, emerging evidence has suggested that obesity become a prevalent health threat worldwide. Reportedly, CTRP9 can ameliorate HFD induced obesity. However, the molecular mechanism underlying the role of CTRP9 in obesity remains elusive. In this study, we reported its major function in the regulation of lipolysis. First, we found that the expression of CTRP9 was decreased in mature adipocytes and white adipose tissue of obese mice. Then, we showed that overexpression adipose tissue CTRP9 alleviated diet-induced obesity and adipocytes hypertrophy, improved glucose intolerance and raised energy expenditure. Moreover, CTRP9 increased the lipolysis in vitro and vivo. Additionally, we determined that CTRP9 enhanced autophagy flux in adipocytes. Intriguingly, knock down Beclin1 by SiRNA abolished the effect of CTRP9 on lipolysis. Mechanically, CTRP9 enhanced the expression of SNX26. We demonstrated that SNX26 was a component of the ATG14L-Beclin1-VPS34 complex and enhanced the assembly of the autophagy-initiation complex. Collectively, our results suggested that CTRP9 alleviated diet induced obesity through enhancing lipolysis mediated by autophagy-initiation complex formation.
摘要：
最近,新出现的证据表明，肥胖成为世界范围内普遍的健康威胁。据报道,CTRP9可以改善HFD诱导的肥胖。然而,CTRP9在肥胖中的作用的分子机制尚不清楚.在这项研究中,我们报道了它在脂解调节中的主要功能。首先,我们发现CTRP9在肥胖小鼠的成熟脂肪细胞和白色脂肪组织中的表达降低。然后，我们发现过表达脂肪组织CTRP9减轻了饮食诱导的肥胖和脂肪细胞肥大，改善葡萄糖不耐受和增加能量消耗。此外，CTRP9在体外和体内增加了脂解作用。此外,我们确定CTRP9增强了脂肪细胞的自噬通量。有趣的是，SiRNA敲除Beclin1消除了CTRP9对脂解的影响。机械上,CTRP9增强了SNX26的表达。我们证明SNX26是ATG14L-Beclin1-VPS34复合物的组成部分，并增强了自噬起始复合物的组装。总的来说，我们的结果表明,CTRP9通过增强自噬起始复合物形成介导的脂解作用,减轻了饮食诱导的肥胖.
