Than Aung, He Hui Ling, Chua Si Hui, Xu Dan, Sun Lei, Leow Melvin Khee-Shing, Chen Peng
From the Bioengineering Program, School of Chemical and Biomedical Engineering, Nanyang Technological University, 70 Nanyang Drive, Singapore 637457.
the Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, and.
J Biol Chem. 2015 Jun 5;290(23):14679-91. doi: 10.1074/jbc.M115.643817. Epub 2015 Apr 30.
Brown adipose tissue expends energy in the form of heat via the mitochondrial uncoupling protein UCP1. Recent studies showed that brown adipose tissue is present in adult humans and may be exploited for its anti-obesity and anti-diabetes actions. Apelin is an adipocyte-derived hormone that plays important roles in energy metabolism. Here, we report that apelin-APJ signaling promotes brown adipocyte differentiation by increasing the expressions of brown adipogenic and thermogenic transcriptional factors via the PI3K/Akt and AMPK signaling pathways. It is also found that apelin relieves the TNFα inhibition on brown adipogenesis. In addition, apelin increases the basal activity of brown adipocytes, as evidenced by the increased PGC1α and UCP1 expressions, mitochondrial biogenesis, and oxygen consumption. Finally, we provide both in vitro and in vivo evidence that apelin is able to increase the brown-like characteristics in white adipocytes. This study, for the first time, reveals the brown adipogenic and browning effects of apelin and suggests a potential therapeutic route to combat obesity and related metabolic disorders.
棕色脂肪组织通过线粒体解偶联蛋白UCP1以热量的形式消耗能量。最近的研究表明，棕色脂肪组织存在于成年人体内，并且因其抗肥胖和抗糖尿病作用而可能得到利用。阿片肽是一种脂肪细胞衍生的激素，在能量代谢中起重要作用。在此，我们报告阿片肽-APJ信号通路通过PI3K/Akt和AMPK信号通路增加棕色脂肪生成和产热转录因子的表达，从而促进棕色脂肪细胞分化。还发现阿片肽可减轻TNFα对棕色脂肪生成的抑制作用。此外，阿片肽增加棕色脂肪细胞的基础活性，PGC1α和UCP1表达增加、线粒体生物发生以及氧消耗增加证明了这一点。最后，我们提供了体外和体内证据，证明阿片肽能够增加白色脂肪细胞中的棕色样特征。本研究首次揭示了阿片肽的棕色脂肪生成和褐变作用，并提出了一条对抗肥胖和相关代谢紊乱的潜在治疗途径。
