美国斯坦福大学医学院Jonathan Z. Long和贝勒医学院Yong Xu研究组合作取得一项新成果。经过不懈努力，他们发现运动产生的一种代谢物可抑制进食和肥胖。2022年6月15日出版的《自然》杂志发表了这项成果。
研究表明运动会刺激N-乳酰苯丙氨酸(Lac-Phe)的产生，这是一种抑制进食和肥胖的血源性信号代谢产物。通过乳酸和苯丙氨酸产生Lac-Phe的过程发生在CNDP2+细胞中，包括巨噬细胞、单核细胞和其他定位于不同器官的免疫细胞和上皮细胞。在饮食诱导的肥胖小鼠中，通过药物增加Lac-Phe的含量会减少食物摄入，而不会影响运动或能量消耗。长期服用Lac-Phe可降低肥胖和体重并改善葡萄糖稳态。相反，敲除小鼠体内与Lac-Phe生物合成相关基因会增加运动训练后的食物摄入和肥胖。
最后，在人类和赛马中也观察到运动会明显增加循环Lac-Phe的量，表明这种代谢物是与多种运动方式和哺乳动物身体活动相关的分子效应物。这些数据揭示了一种保守的运动诱导代谢物，它控制食物摄入并影响系统能量平衡。
据悉，运动可以预防肥胖型糖尿病和其他心脏代谢疾病。然而，运动产生有益于代谢的分子和细胞机制仍不清楚。
附：英文原文
Title: An exercise-inducible metabolite that suppresses feeding and obesity
Author: Li, Veronica L., He, Yang, Contrepois, Kvin, Liu, Hailan, Kim, Joon T., Wiggenhorn, Amanda L., Tanzo, Julia T., Tung, Alan Sheng-Hwa, Lyu, Xuchao, Zushin, Peter-James H., Jansen, Robert S., Michael, Basil, Loh, Kang Yong, Yang, Andrew C., Carl, Christian S., Voldstedlund, Christian T., Wei, Wei, Terrell, Stephanie M., Moeller, Benjamin C., Arthur, Rick M., Wallis, Gareth A., van de Wetering, Koen, Stahl, Andreas, Kiens, Bente, Richter, Erik A., Banik, Steven M., Snyder, Michael P., Xu, Yong, Long, Jonathan Z.
Issue&Volume: 2022-06-15
Abstract: Exercise confers protection against obesity, type2 diabetes and other cardiometabolic diseases1,2,3,4,5. However, the molecular and cellular mechanisms that mediate the metabolic benefits of physical activity remain unclear6. Here we show that exercise stimulates the production of N-lactoyl-phenylalanine (Lac-Phe), a blood-borne signalling metabolite that suppresses feeding and obesity. The biosynthesis of Lac-Phe from lactate and phenylalanine occurs in CNDP2+ cells, including macrophages, monocytes and other immune and epithelial cells localized to diverse organs. In diet-induced obese mice, pharmacological-mediated increases in Lac-Phe reduces food intake without affecting movement or energy expenditure. Chronic administration of Lac-Phe decreases adiposity and body weight and improves glucose homeostasis. Conversely, genetic ablation of Lac-Phe biosynthesis in mice increases food intake and obesity following exercise training. Last, large activity-inducible increases in circulating Lac-Phe are also observed in humans and racehorses, establishing this metabolite as a molecular effector associated with physical activity across multiple activity modalities and mammalian species. These data define a conserved exercise-inducible metabolite that controls food intake and influences systemic energy balance.
DOI: 10.1038/s41586-022-04828-5
Source: https://www.nature.com/articles/s41586-022-04828-5
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
