| First Author | Wei W | Year | 2024 |
| Journal | Nature | Volume | 633 |
| Issue | 8028 | Pages | 182-188 |
| PubMed ID | 39112712 | Mgi Jnum | J:354335 |
| Mgi Id | MGI:7731024 | Doi | 10.1038/s41586-024-07801-6 |
| Citation | Wei W, et al. (2024) PTER is a N-acetyltaurine hydrolase that regulates feeding and obesity. Nature 633(8028):182-188 |
| abstractText | 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. |
