An exercise-inducible metabolite that suppresses feeding and obesity
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An exercise-inducible metabolite that suppresses feeding and obesity. / 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 Strini; Voldstedlund, Christian Thomas; 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.
In: Nature, Vol. 606, 2022, p. 785-790.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - An exercise-inducible metabolite that suppresses feeding and obesity
AU - Li, Veronica L
AU - He, Yang
AU - Contrepois, Kévin
AU - Liu, Hailan
AU - Kim, Joon T
AU - Wiggenhorn, Amanda L
AU - Tanzo, Julia T
AU - Tung, Alan Sheng Hwa
AU - Lyu, Xuchao
AU - Zushin, Peter James H
AU - Jansen, Robert S
AU - Michael, Basil
AU - Loh, Kang Yong
AU - Yang, Andrew C.
AU - Carl, Christian Strini
AU - Voldstedlund, Christian Thomas
AU - Wei, Wei
AU - Terrell, Stephanie M
AU - Moeller, Benjamin C
AU - Arthur, Rick M
AU - Wallis, Gareth A
AU - van de Wetering, Koen
AU - Stahl, Andreas
AU - Kiens, Bente
AU - Richter, Erik A.
AU - Banik, Steven M
AU - Snyder, Michael P.
AU - Xu, Yong
AU - Long, Jonathan Z
N1 - Publisher Copyright: © 2022, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Faculty of Science
KW - Metabolomics
KW - Obesity
KW - Proteases
KW - Lac-Phe
U2 - 10.1038/s41586-022-04828-5
DO - 10.1038/s41586-022-04828-5
M3 - Journal article
C2 - 35705806
AN - SCOPUS:85131943233
VL - 606
SP - 785
EP - 790
JO - Nature
JF - Nature
SN - 0028-0836
ER -
ID: 311128545