| First Author | Li VL | Year | 2022 |
| Journal | Nature | Volume | 606 |
| Issue | 7915 | Pages | 785-790 |
| PubMed ID | 35705806 | Mgi Jnum | J:330569 |
| Mgi Id | MGI:7367070 | Doi | 10.1038/s41586-022-04828-5 |
| Citation | Li VL, et al. (2022) An exercise-inducible metabolite that suppresses feeding and obesity. Nature 606(7915):785-790 |
| abstractText | 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. |
