An exercise-inducible metabolite that suppresses feeding and obesity.

Autor: Li VL; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Department of Chemistry, Stanford University, Stanford, CA, USA.; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.; Wu Tsai Human Performance Alliance, Stanford University, Stanford, CA, USA., He Y; Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Contrepois K; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.; Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA.; Stanford Diabetes Research Center, Stanford University, Stanford, CA, USA., Liu H; Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Kim JT; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Sarafan ChEM-H, Stanford University, Stanford, CA, USA., Wiggenhorn AL; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Department of Chemistry, Stanford University, Stanford, CA, USA.; Sarafan ChEM-H, Stanford University, Stanford, CA, USA., Tanzo JT; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Sarafan ChEM-H, Stanford University, Stanford, CA, USA., Tung AS; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Sarafan ChEM-H, Stanford University, Stanford, CA, USA., Lyu X; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.; Wu Tsai Human Performance Alliance, Stanford University, Stanford, CA, USA., Zushin PH; Department of Nutrition and Toxicology, University of California Berkeley, Berkeley, CA, USA., Jansen RS; Netherlands Cancer Institute, Amsterdam, Netherlands.; Department of Microbiology, Radboud University, Nijmegen, Netherlands., Michael B; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA., Loh KY; Department of Chemistry, Stanford University, Stanford, CA, USA.; Sarafan ChEM-H, Stanford University, Stanford, CA, USA., Yang AC; Department of Anatomy and the Bakar Aging Research Institute, University of California San Francisco, San Francisco, CA, USA., Carl CS; August Krogh Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark., Voldstedlund CT; August Krogh Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark., Wei W; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.; Department of Biology, Stanford University, Stanford, CA, USA., Terrell SM; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Sarafan ChEM-H, Stanford University, Stanford, CA, USA., Moeller BC; Maddy Equine Analytical Chemistry Laboratory, California Animal Health and Food Safety Laboratory, School of Veterinary Medicine, University of California at Davis, Davis, CA, USA.; Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA., Arthur RM; Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA., Wallis GA; School of Sport, Exercise, and Rehabilitation Sciences, College of Life and Environmental Sciences, University of Birmingham, Birmingham, UK., van de Wetering K; Netherlands Cancer Institute, Amsterdam, Netherlands.; Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, PA, USA., Stahl A; Department of Nutrition and Toxicology, University of California Berkeley, Berkeley, CA, USA., Kiens B; August Krogh Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark., Richter EA; August Krogh Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark., Banik SM; Department of Chemistry, Stanford University, Stanford, CA, USA.; Sarafan ChEM-H, Stanford University, Stanford, CA, USA., Snyder MP; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.; Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA.; Stanford Diabetes Research Center, Stanford University, Stanford, CA, USA.; Wu Tsai Human Performance Alliance, Stanford University, Stanford, CA, USA., Xu Y; Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA. yongx@bcm.edu.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA. yongx@bcm.edu., Long JZ; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. jzlong@stanford.edu.; Sarafan ChEM-H, Stanford University, Stanford, CA, USA. jzlong@stanford.edu.; Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA. jzlong@stanford.edu.; Stanford Diabetes Research Center, Stanford University, Stanford, CA, USA. jzlong@stanford.edu.; Wu Tsai Human Performance Alliance, Stanford University, Stanford, CA, USA. jzlong@stanford.edu.
Jazyk: angličtina
Zdroj: Nature [Nature] 2022 Jun; Vol. 606 (7915), pp. 785-790. Date of Electronic Publication: 2022 Jun 15.
DOI: 10.1038/s41586-022-04828-5
Abstrakt: Exercise confers protection against obesity, type 2 diabetes and other cardiometabolic diseases 1-5 . However, the molecular and cellular mechanisms that mediate the metabolic benefits of physical activity remain unclear 6 . 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.
(© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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