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In endogenous taurine metabolism, dedicated enzymes are involved in the biosynthesis of taurine from cysteine and in the downstream metabolism of secondary taurine metabolites<jats:sup>4,5<\/jats:sup>. One taurine metabolite is <jats:italic>N<\/jats:italic>-acetyltaurine<jats:sup>6<\/jats:sup>. Levels of <jats:italic>N<\/jats:italic>-acetyltaurine are dynamically regulated by stimuli that alter taurine or acetate flux, including endurance exercise<jats:sup>7<\/jats:sup>, dietary taurine supplementation<jats:sup>8<\/jats:sup> and alcohol consumption<jats:sup>6,9<\/jats:sup>. So far, the identities of the enzymes involved in <jats:italic>N<\/jats:italic>-acetyltaurine metabolism, and the potential functions of <jats:italic>N<\/jats:italic>-acetyltaurine itself, have remained unknown. Here we show that the body\u00a0mass\u00a0index\u00a0associated orphan enzyme phosphotriesterase-related (PTER)<jats:sup>10<\/jats:sup> is a physiological <jats:italic>N<\/jats:italic>-acetyltaurine hydrolase. In vitro, PTER catalyses the hydrolysis of <jats:italic>N<\/jats:italic>-acetyltaurine to taurine and acetate. In mice, PTER is expressed in the kidney, liver and brainstem. Genetic ablation of <jats:italic>Pter<\/jats:italic> in mice results in complete loss of tissue <jats:italic>N<\/jats:italic>-acetyltaurine hydrolysis activity and a systemic increase in <jats:italic>N<\/jats:italic>-acetyltaurine levels. After stimuli that increase taurine levels, <jats:italic>Pter<\/jats:italic> knockout mice exhibit reduced food intake, resistance to diet-induced obesity and improved glucose homeostasis. Administration of <jats:italic>N<\/jats:italic>-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 <jats:italic>N<\/jats:italic>-acetyltaurine in body weight control and energy balance.<\/jats:p>","DOI":"10.1038\/s41586-024-07801-6","type":"journal-article","created":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T16:14:48Z","timestamp":1723047288000},"page":"182-188","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["PTER is a N-acetyltaurine hydrolase that regulates feeding and 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