Work

Lac-Phe: a central metabolic regulator and biomarker

Year: 2025

Type: article

Abstract: N-lactoyl-phenylalanine (Lac-Phe), an exercise-induced metabolite that suppresses appetite, has quickly emerged as a key molecule in metabolic signaling networks. Lac-Phe, following its CNDP2-mediated synthesis, mediates key appetite- and weight-modulating effects of metformin, which acts primarily by mitochondrial inhibition in gut epithelial cells. Both Lac-Phe and related N-lactoyl-amino acids serve as potent biomarkers of mitochondrial dysfunction. Elevated levels of these metabolites are found in genetic mitochondrial diseases, offering potentially superior prognostic value compared to lactate in conditions alike. Despite uncertainties regarding its specific receptor(s) and signaling mechanisms, the expanding roles of Lac-Phe underscore its critical position at the intersection of exercise physiology, pharmacology, energy metabolism, and disease pathology, suggesting significant potential for future diagnostics and therapeutics in mitochondrial and metabolic disorders.

Source: Medical Review

DOI: 10.1515/mr-2025-0030

Authors: Taikang Yao, Guolin Alexander Wen, Zhenchao Wu, Ning Shen

Institutions: Peking University, Peking University Third Hospital, Harvard University, Massachusetts General Hospital, Dana-Farber Cancer Institute

Language: English

Topic: Metabolism, Diabetes, and Cancer

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: diamond

Funders: Peking University, Peking University Third Hospital