- Lac-Phe is a conserved, rapidly increased exercise-induced metabolite that functions as a bioactive mediator linking exercise to systemic metabolic benefits.
- Biosynthesis and excretion follow a defined two-step pathway, establishing mechanisms for Lac-Phe production and regulated release into circulation.
- Lac-Phe signals peripheral metabolism to central appetite and energy circuits and shows promise as a biomarker and therapeutic target in disease.
Annu Rev Nutr. 2026 Aug;46(1):153-175. doi: 10.1146/annurev-nutr-061824-054717.
ABSTRACT
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.
PMID:42629319 | DOI:10.1146/annurev-nutr-061824-054717
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