Betatrophin knockdown induces beiging and mitochondria biogenesis of white adipocytes
Betatrophin knockdown induces beiging and mitochondria biogenesis of white adipocytes
复制标题
Betatropin 敲低诱导白色脂肪细胞的米色和线粒体生物合成
DOI：
10.1530/joe-19-0447
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发表时间：
2020-04-01
影响因子：
4
通讯作者：
Xiao, Xin-Hua
中科院分区：
文献类型：
--
作者：
Liao, Zhe-Zhen;Qi, Xiao-Yan;Xiao, Xin-Hua
将储存能量的白色脂肪重塑为消耗能量的米色脂肪，这为减轻肥胖症提供了一种很有前途的新方法。一些研究表明脂肪因子可以通过自分泌或旁分泌作用诱导白色脂肪组织（WAT）褐变。Betatrophin是一种新型脂肪因子，与能量消耗和脂肪分解有关，但尚未明确阐明。在这里，我们使用高脂饮食诱导的肥胖症，以确定如何betatrophin调节肥胖和肥胖。我们发现，β-营养素基因敲除小鼠显示出较少的白色脂肪量和降低的血浆TG和NEFA水平。因此，抑制betatrophin导致脂肪细胞的表型改变，其特征在于在体内和体外增加线粒体含量、米色脂肪细胞和线粒体生物发生特异性标志物。值得注意的是，阻断AMP-活化蛋白激酶（AMPK）信号传导途径能够消除betatrophin敲低脂肪细胞中增强的米色样特征。总的来说，betatrophin的下调通过AMPK信号通路的激活诱导白色脂肪细胞中的beiging。这些过程表明β-肌营养素是肥胖症的潜在治疗靶点。
Remodeling of energy-storing white fat into energy-consuming beige fat has led to a promising new approach to alleviate adiposity. Several studies have shown adipokines can induce white adipose tissue (WAT) beiging through autocrine or paracrine actions. Betatrophin, a novel adipokine, has been linked to energy expenditure and lipolysis but not clearly clarified. Here, we using high-fat diet-induced obesity to determine how betatrophin modulate beiging and adiposity. We found that betatrophin-knockdown mice displayed less white fat mass and decreased plasma TG and NEFA levels. Consistently, inhibition of betatrophin leads to the phenotype change of adipocytes characterized by increased mitochondria contents, beige adipocytes and mitochondria biogenesis-specific markers both in vivo and in vitro. Of note, blocking AMP-activated protein kinase (AMPK) signaling pathway is able to abolish enhanced beige-like characteristics in betatrophin-knockdown adipocytes. Collectively, downregulation of betatrophin induces beiging in white adipocytes through activation of AMPK signaling pathway. These processes suggest betatrophin as a latent therapeutic target for obesity.