Publications

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

  Wei W., Lyu X., Markhard A.L., Fu S., Mardjuki R.E., Cavanagh P.E., Zeng X., Rajniak J., Lu N., Xiao S., Zhao M., Moya-Garzon M.D., Truong S.D., Chou J.C., Wat L.W., Chidambaranathan-Reghupaty S., Coassolo L., Xu D., Shen F., Huang W., Ramirez C.B., Jang C., Li L., Svensson K.J., Fischbach M.A., Long J.Z.

  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<sup>4 ... >> More

  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-acetyltaurine⁶. Levels of N-acetyltaurine are dynamically regulated by stimuli that alter taurine or acetate flux, including endurance exercise⁷, dietary taurine supplementation⁸ 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. << Less

  Nature 0:0-0(2024) [PubMed] [EuropePMC]

  This publication is cited by 5 other entries.