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

Wei Wei, Xuchao Lyu, Andrew L. Markhard, Sipei Fu, Rachel E. Mardjuki, Peter E. Cavanagh, Xianfeng Zeng, Jakub Rajniak, Nannan Lu, Shuke Xiao, Meng Zhao, Maria Dolores Moya-Garzon, Steven D. Truong, Jonathan Chiu‐Chun Chou, Lianna W. Wat, Saranya Chidambaranathan-Reghupaty, Laetitia Coassolo, Duo Xu, Fangfang Shen, Wentao Huang, Cuauhtemoc B. Ramirez, Cholsoon Jang, Lingyin Li, Katrin J. Svensson, Michael A. Fischbach and Jonathan Z. Long ()
Additional contact information
Wei Wei: Stanford University School of Medicine
Xuchao Lyu: Stanford University School of Medicine
Andrew L. Markhard: Stanford University School of Medicine
Sipei Fu: Stanford University School of Medicine
Rachel E. Mardjuki: Stanford University
Peter E. Cavanagh: Stanford University
Xianfeng Zeng: Stanford University
Jakub Rajniak: Stanford University
Nannan Lu: Stanford University
Shuke Xiao: Stanford University School of Medicine
Meng Zhao: Stanford University School of Medicine
Maria Dolores Moya-Garzon: Stanford University School of Medicine
Steven D. Truong: Stanford University School of Medicine
Jonathan Chiu‐Chun Chou: Stanford University
Lianna W. Wat: Stanford University School of Medicine
Saranya Chidambaranathan-Reghupaty: Stanford University School of Medicine
Laetitia Coassolo: Stanford University School of Medicine
Duo Xu: Stanford University
Fangfang Shen: Stanford University
Wentao Huang: Massachusetts Institute of Technology
Cuauhtemoc B. Ramirez: University of California Irvine
Cholsoon Jang: University of California Irvine
Lingyin Li: Stanford University
Katrin J. Svensson: Stanford University School of Medicine
Michael A. Fischbach: Stanford University
Jonathan Z. Long: Stanford University School of Medicine

Nature, 2024, vol. 633, issue 8028, 182-188

Abstract: Abstract 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 supplementation8 and 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)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.

Date: 2024
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DOI: 10.1038/s41586-024-07801-6

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