학술논문
An exercise-inducible metabolite that suppresses feeding and obesity.
Document Type
article
Author
Li, Veronica L; He, Yang; Contrepois, Kévin; 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
Source
Nature. 606(7915)
Subject
Language
Abstract
Exercise confers protection against obesity, type 2 diabetes and other cardiometabolic diseases1-5. 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.