Department of Metabolism and Endocrinology, The First Affiliated Hospital of University of South China, Hengyang, Hunan Province, China.
J Endocrinol. 2020 Apr;245(1):93-100. doi: 10.1530/JOE-19-0447.
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.
将储能白色脂肪重塑为耗能米色脂肪，为减轻肥胖症提供了一种有前途的新方法。多项研究表明，脂肪细胞因子可通过自分泌或旁分泌作用诱导白色脂肪组织（WAT）褐变。betatrophin 是一种新型脂肪细胞因子，与能量消耗和脂肪分解有关，但尚未得到明确阐明。在这里，我们使用高脂肪饮食诱导肥胖来确定 betatrophin 如何调节褐变和肥胖。我们发现，betatrophin 敲低小鼠的白色脂肪质量减少，血浆 TG 和 NEFA 水平降低。一致地，抑制 betatrophin 导致脂肪细胞表型改变，其特征是体内和体外的线粒体含量增加、米色脂肪细胞和线粒体生物发生特异性标志物增加。值得注意的是，阻断 AMP 激活的蛋白激酶（AMPK）信号通路能够消除 betatrophin 敲低脂肪细胞中增强的米色样特征。总之，下调 betatrophin 通过激活 AMPK 信号通路诱导白色脂肪细胞褐变。这些过程表明 betatrophin 是肥胖症的潜在治疗靶点。
