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

Autor: 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.
Zdroj: Nature; September 2024, Vol. 633 Issue: 8028 p182-188, 7p
Abstrakt: Taurine is a conditionally essential micronutrient and one of the most abundant amino acids in humans1–3. In endogenous taurine metabolism, dedicated enzymes are involved in the biosynthesis of taurine from cysteine and in the downstream metabolism of secondary taurine metabolites4,5. One taurine metabolite is N-acetyltaurine6. Levels of N-acetyltaurine are dynamically regulated by stimuli that alter taurine or acetate flux, including endurance exercise7, dietary taurine supplementation8and alcohol consumption6,9. 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)10is 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 Pterin 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, Pterknockout 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.
Databáze: Supplemental Index
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