2. Academic Validation
  3. PTER is a N-acetyltaurine hydrolase that regulates feeding and obesity

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

  • Nature. 2024 Sep;633(8028):182-188. doi: 10.1038/s41586-024-07801-6.
Wei Wei 1 2,  Xuchao Lyu 1 2 3,  Andrew L Markhard 1 2,  Sipei Fu 1 2 4,  Rachel E Mardjuki 2 5 6,  Peter E Cavanagh 5,  Xianfeng Zeng 2 7,  Jakub Rajniak 2 7,  Nannan Lu 8 9,  Shuke Xiao 1 2,  Meng Zhao 1 10,  Maria Dolores Moya-Garzon 1 2 3,  Steven D Truong 1 2,  Jonathan Chiu-Chun Chou 6,  Lianna W Wat 1 10 11,  Saranya Chidambaranathan-Reghupaty 1 10 11,  Laetitia Coassolo 1 10 11,  Duo Xu 2 5,  Fangfang Shen 2 6,  Wentao Huang 12,  Cuauhtemoc B Ramirez 13,  Cholsoon Jang 13,  Lingyin Li 2 5 14,  Katrin J Svensson 1 10 11,  Michael A Fischbach 2 7,  Jonathan Z Long 15 16 17 18 19 20
Affiliations

Affiliations

  • 1 Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • 2 Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
  • 3 Wu Tsai Human Performance Alliance, Stanford University, Stanford, CA, USA.
  • 4 Department of Biology, Stanford University, Stanford, CA, USA.
  • 5 Department of Biochemistry, Stanford University, Stanford, CA, USA.
  • 6 Department of Chemistry, Stanford University, Stanford, CA, USA.
  • 7 Department of Bioengineering, Stanford University, Stanford, CA, USA.
  • 8 Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.
  • 9 Wu Tsai Neurosciences Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • 10 Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA, USA.
  • 11 Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • 12 Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • 13 Department of Biological Chemistry, University of California Irvine, Irvine, CA, USA.
  • 14 Arc Institute, Palo Alto, CA, USA.
  • 15 Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. [email protected].
  • 16 Sarafan ChEM-H, Stanford University, Stanford, CA, USA. [email protected].
  • 17 Wu Tsai Human Performance Alliance, Stanford University, Stanford, CA, USA. [email protected].
  • 18 Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA, USA. [email protected].
  • 19 Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA. [email protected].
  • 20 The Phil and Penny Knight Initiative for Brain Resilience at the Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA. [email protected].
PMID: 39112712 DOI: 10.1038/s41586-024-07801-6
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.

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