能量稳态
平衡
弓状核
线粒体
葡萄糖稳态
下丘脑
受体
生物
弧(几何)
丙种皮质醇
内科学
内分泌学
细胞生物学
胰岛素抵抗
胰岛素
医学
生物化学
几何学
数学
作者
Seul Ki Kim,Le Trung Tran,Churl Namkoong,Hyung Jin Choi,Hye Jin Chun,Yong‐ho Lee,Myunghyun Cheon,ChiHye Chung,Junmo Hwang,Hyun–Ho Lim,Dong Min Shin,Yun‐Hee Choi,Ki Woo Kim
标识
DOI:10.1038/s41467-023-40082-7
摘要
Abstract Small humanin-like peptide 2 (SHLP2) is a mitochondrial-derived peptide implicated in several biological processes such as aging and oxidative stress. However, its functional role in the regulation of energy homeostasis remains unclear, and its corresponding receptor is not identified. Hereby, we demonstrate that both systemic and intracerebroventricular (ICV) administrations of SHLP2 protected the male mice from high-fat diet (HFD)-induced obesity and improved insulin sensitivity. In addition, the activation of pro-opiomelanocortin (POMC) neurons by SHLP2 in the arcuate nucleus of the hypothalamus (ARC) is involved in the suppression of food intake and the promotion of thermogenesis. Through high-throughput structural complementation screening, we discovered that SHLP2 binds to and activates chemokine receptor 7 (CXCR7). Taken together, our study not only reveals the therapeutic potential of SHLP2 in metabolic disorders but also provides important mechanistic insights into how it exerts its effects on energy homeostasis.
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