Abstract

Abstract Taurine is a conditionally essential micronutrient and one of the most abundant amino acids in humans 1–3 . 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.