美国斯坦福大学Jonathan Z. Long和Michael A. Fischbach研究组的论文发现，PTER是一种调节进食和肥胖的N-乙酰牛磺酸水解酶。2024年8月7日，国际知名学术期刊《自然》发表了这一成果。

研究表明，与体重指数相关的磷酸三酯酶相关蛋白(PTER)是一种生理N-乙酰牛磺酸水解酶。在体外，PTER催化N-乙酰牛磺酸水解为牛磺酸和乙酸酯。在小鼠中，PTER在肾脏、肝脏和脑干中表达。小鼠Pter基因敲除导致组织N-乙酰牛磺酸水解活性完全丧失，N-乙酰牛磺酸水平系统性升高。

在刺激增加牛磺酸水平后，Pter基因敲除小鼠表现出食物摄入量减少，对饮食引起的肥胖有抵抗力，葡萄糖稳态改善。对肥胖野生型小鼠给予N-乙酰牛磺酸也以GFRAL依赖的方式减少食物摄入量和体重。这些数据将PTER置于次级牛磺酸代谢的中心酶节点，并揭示了PTER和N-乙酰牛磺酸在体重控制和能量平衡中的作用。

据悉，牛磺酸是一种有条件必需的微量营养素，也是人体中最丰富的氨基酸之一。在内源性牛磺酸代谢中，专门的酶参与了半胱氨酸对牛磺酸的生物合成以及次级牛磺酸代谢物的下游代谢。

牛磺酸的代谢物之一是N-乙酰牛磺酸。N-乙酰牛磺酸的水平受到改变牛磺酸或醋酸酯通量的刺激动态调节，包括耐力运动、饮食中补充牛磺酸和饮酒。迄今为止，参与N-乙酰牛磺酸代谢的酶的身份以及N-乙酰牛磺酸本身的潜在功能仍不清楚。

附：英文原文

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

Author: Wei, Wei, Lyu, Xuchao, Markhard, Andrew L., Fu, Sipei, Mardjuki, Rachel E., Cavanagh, Peter E., Zeng, Xianfeng, Rajniak, Jakub, Lu, Nannan, Xiao, Shuke, Zhao, Meng, Moya-Garzon, Maria Dolores, Truong, Steven D., Chou, Jonathan ChiuChun, Wat, Lianna W., Chidambaranathan-Reghupaty, Saranya, Coassolo, Laetitia, Xu, Duo, Shen, Fangfang, Huang, Wentao, Ramirez, Cuauhtemoc B., Jang, Cholsoon, Li, Lingyin, Svensson, Katrin J., Fischbach, Michael A., Long, Jonathan Z.

Issue&Volume: 2024-08-07

Abstract: Taurine is a conditionally essential micronutrient and one of the most abundant amino acids in humans1,2,3. 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.

DOI: 10.1038/s41586-024-07801-6

Source: https://www.nature.com/articles/s41586-024-07801-6