The benefits of exercise in mitigating obesity, type 2 diabetes, and other cardiometabolic diseases are well-established, but the underlying molecular and cellular mechanisms remain elusive. Join us in this episode as we explore these mechanisms with Dr. Long, whose research has led to the discovery of N-lactoyl-phenylalanine (Lac-Phe), a metabolite stimulated by exercise that suppresses feeding and obesity.

Dr. Long's team found that Lac-Phe is synthesized from lactate and phenylalanine in CNDP2+ cells, including macrophages, monocytes, and other immune and epithelial cells found in various organs. In diet-induced obese mice, an increase in Lac-Phe levels reduced food intake, leading to decreased adiposity and body weight, and improved glucose homeostasis. They further discovered that ablation of Lac-Phe biosynthesis resulted in increased food intake and obesity post-exercise training.

Importantly, the research also demonstrated that circulating Lac-Phe levels rise considerably with physical activity in humans and racehorses, indicating its role as a conserved molecular effector across different mammalian species. Tune in as we delve into how Dr. Long's pioneering work could redefine our understanding of exercise's role in metabolic health.

Keywords: Exercise, Obesity, Type 2 Diabetes, N-lactoyl-phenylalanine, Metabolic Health, Dr. Long.

Li, V.L., He, Y., Contrepois, K. et al. An exercise-inducible metabolite that suppresses feeding and obesity. Nature (2022). https://doi.org/10.1038/s41586-022-04828-5