PTER is a N-acetyltaurine hydrolase that regulates feeding and obesity

• 成果类型: Article
• 署名作者: Wei, Wei; Lyu, Xuchao; Markhard, Andrew L.; Fu, Sipei; Mardjuki, Rachel E.; Cavanagh, Peter E.; Zeng, Xianfeng; Rajniak, Jakub; Lu, Nannan; Xiao, Shuke; Zhao, Meng; Moya-Garzon, Maria Dolores; Truong, Steven D.; Chou, Jonathan Chiu-Chun; Wat, Lianna W.; Chidambaranathan-Reghupaty, Saranya; Coassolo, Laetitia; Xu, Duo; Shen, Fangfang; Huang, Wentao; Ramirez, Cuauhtemoc B.; Jang, Cholsoon; Li, Lingyin; Svensson, Katrin J.; Fischbach, Michael A.; Long, Jonathan Z.
• 署名单位: Stanford University; Stanford University; Stanford University; Stanford University; Stanford University; Stanford University; Stanford University; Stanford University; Stanford University; Stanford University; Massachusetts Institute of Technology (MIT); Stanford University; University of California System; University of California Irvine; Stanford University
• 刊物名称: Nature
• ISSN/ISSBN: 0028-3917
• DOI: 10.1038/s41586-024-07801-6
• 发表日期: 2024-09-05
• 关键词: taurine transporter knockout; skeletal-muscle; amino-acids; expression; ethanol; cloning

摘要

Taurine is a conditionally essential micronutrient and one of the most abundant amino acids in humans(1,2,3). In endogenous taurine metabolism, dedicated enzymes are involved in the biosynthesis of taurine from cysteine and in the downstream metabolism of secondary taurine metabolites(4,5). One taurine metabolite is N-acetyltaurine(6). Levels of N-acetyltaurine are dynamically regulated by stimuli that alter taurine or acetate flux, including endurance exercise(7), dietary taurine supplementation(8) and alcohol consumption(6,9). So far, the identities of the enzymes involved in N-acetyltaurine metabolism, and the potential functions of N-acetyltaurine itself, have remained unknown. Here we show that the body mass index associated orphan enzyme phosphotriesterase-related (PTER)(10) is a physiological N-acetyltaurine hydrolase. In vitro, PTER catalyses the hydrolysis of N-acetyltaurine to taurine and acetate. In mice, PTER is expressed in the kidney, liver and brainstem. Genetic ablation of Pter in mice results in complete loss of tissue N-acetyltaurine hydrolysis activity and a systemic increase in N-acetyltaurine levels. After stimuli that increase taurine levels, Pter knockout mice exhibit reduced food intake, resistance to diet-induced obesity and improved glucose homeostasis. Administration of N-acetyltaurine to obese wild-type mice also reduces food intake and body weight in a GFRAL-dependent manner. These data place PTER into a central enzymatic node of secondary taurine metabolism and uncover a role for PTER and N-acetyltaurine in body weight control and energy balance.