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2.d.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS10408/FILES/KO_heart_ 1.d.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS10408/FILES/KO_eWAT_ 3.d.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS10408/FILES/KO_gut_ 2.d.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS10408/FILES/KO_lung_ 2.d.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS10408/FILES/KO_BAT_ 3.d.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS10408/FILES/WT_kidney__ 1.d.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS10408/FILES/KO_kidney_ 2.d.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS10408/FILES/WT_iWAT__ 1.d.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS10408/FILES/WT_BAT__ 3.d.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS10408/FILES/WT_blood__ 2.d.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS10408/FILES/WT_quad__ 3.d.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS10408/FILES/WT_eWAT__ 1.d.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS10408/FILES/KO_pancreas_ 2.d.zipprimaryOK200ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS10408<p>N-acetyltaurine (Cayman, 35169) eluted around 12 min and taurine (sigma, T0625-500G) eluted around 13 min under the above conditions.</p>MetaboLightsPublicLiquid Chromatography MS - negative - hilic<p>The separation of polar metabolites was conducted using a Luna 5 μm NH2 100 Å LC column (Phenomenex 00B-4378-E0) with normal phase chromatography. Mobile phases were as follows: buffer A, 95:5 water:acetonitrile with 0.2% ammonium hydroxide and 10 mM ammonium acetate; buffer B, acetonitrile. The LC gradient initiated at 100% B with a flow rate of 0.2 mL/min from 0 to 2 min. The gradient was then linearly increased to 50% A/50% B at a flow rate of 0.7 mL/min from 2 to 20 min. From 20 to 25 min, the gradient was maintained at 50% A/50% B at a flow rate of 0.7 mL/min.</p>PTER is a N-acetyltaurine hydrolase that regulates feeding and obesity. 10.1038/s41586-024-07801-6. PMID:39112712Wei WeiStanford Universitylungkidneyquadricepsintestineblood plasmabrown adipose tissuewhite adipose tissuespleenliverpancreasbrainheartmass spectrometry<p>Metabolites were extracted with 1:2:1 (tissue:ACN:methonal) and spun down at 20,000 rpm for 1 h. Supernatant was collected and injected into a LC-MS.</p>Mus musculushttps://www.ebi.ac.uk/metabolights/MTBLS10408Wei Wei. Stanford University. 290 Jane Stanford Way, Palo Alto, CA, USA 94305. wwbiomed@stanford.edu.Jonathan Long. Stanford University. 290 Jane Stanford Way, Palo Alto, California, USA 94305. jzlong@stanford.edu.<p>Data were stored as Agilent .d files and analyzed using the Agilent Qualitative Analysis 10.0 software.</p>TissueGenotypewwbiomed@stanford.edu<p>Tissues were collected from mice and stored immediately at -80 °C for future use.</p>MetabolomicsHydrolasetaurineuntargeted metabolitesobesityHydrolasetaurineuntargeted metabolitesobesity<p>Metabolite measurements were performed using an Agilent 6520 Quadrupole time-of-flight LC–MS instrument as previously described[29]. MS analysis was performed using electrospray ionization (ESI) in negative mode. The dual ESI source parameters were configured as follows: the gas temperature was maintained at 250 °C with a drying gas flow of 12 L/min and the nebulizer pressure at 20 psi; the capillary voltage was set to 3500 V; and the fragmentor voltage set to 100 V.</p>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.PTER is a N-acetyltaurine hydrolase that regulates feeding and obesity.Wei Wei W, Lyu Xuchao X, Markhard Andrew L AL, Fu Sipei S, Mardjuki Rachel E RE, Cavanagh Peter E PE, Zeng Xianfeng X, Rajniak Jakub J, Lu Nannan N, Xiao Shuke S, Zhao Meng M, Moya-Garzon Maria Dolores MD, Truong Steven D SD, Chou Jonathan Chiu-Chun JC, Wat Lianna W LW, Chidambaranathan-Reghupaty Saranya S, Coassolo Laetitia L, Xu Duo D, Shen Fangfang F, Huang Wentao W, Ramirez Cuauhtemoc B CB, Jang Cholsoon C, Li Lingyin L, Svensson Katrin J KJ, Fischbach Michael A MA, Long Jonathan Z JZfalsePTER is an N-acetyltaurine hydrolase that regulates feeding and obesity<p>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 biosynthesis of taurine from cysteine as well as the downstream metabolism of secondary taurine metabolites4,5. One such 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. To date, the identity of 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 PTER (phosphotriesterase-related)10 is a physiologic N-acetyltaurine hydrolase. In vitro, PTER catalyzes degradation 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 systemic elevation of N-acetyltaurine levels. Upon stimuli that increase taurine levels, PTER-KO 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.</p>2024-09-112024-06-11MTBLS1040839112712