Lac-Phe: An Exercise Hormone for Metabolic Regulation.

N-Lactoyl-phenylalanine (Lac-Phe), a conserved exercise-induced metabolite that rises rapidly in circulation, has emerged as a key molecular mediator linking fundamental metabolism to translational medicine. In this review, we elaborate recent findings that define a two-step framework for Lac-Phe biosynthesis and excretion. Functional studies show that Lac-Phe exerts broad metabolic benefits and should be regarded as a bioactive molecule rather than a passive by-product of intermediary metabolism. Furthermore, we review the neural mechanisms through which Lac-Phe conveys peripheral metabolic cues to central circuits regulating appetite and energy balance. Beyond the role of Lac-Phe in energy balance, alterations in Lac-Phe concentrations are associated with disease pathogenesis and progression, underscoring its potential as both a biomarker and a therapeutic agent. Collectively, these advances position Lac-Phe at the intersection of exercise physiology, metabolism, and disease and thus highlight its potential to integrate metabolic and physiological health.