Lac-Phe (N-lactoyl-phenylalanine) is a conjugate of lactate and phenylalanine and the most abundant member of the N-lactoyl-amino acids. Lac-Phe is formed by CNDP2-mediated condensation of lactate and phenylalanine. Plasma Lac-Phe levels are elevated by diverse stimuli that increase circulating lactate or phenylalanine levels, or increase glycolytic flux, in both mice and humans. These stimuli include sprint exercise, metformin treatment, feeding, phenylketonuria, and mitochondrial disease.
Lac-Phe is an anorexigenic signaling metabolite that suppresses food intake. Pharmacological Lac-Phe injection reduces food intake and adiposity. Genetic ablation of CNDP2 abolishes Lac-Phe biosynthesis and renders the animals resistant to the anti-obesity effects of both exercise and metformin treatment. As a common signaling metabolite stimulated by diverse physiologic stimuli, the role of Lac-Phe beyond energy balance warrants further studies.
