N-acetyl-phenylalanine induces hepatic steatosis in MASLD by disrupting ER-mitochondria calcium coupling and mitochondrial lipid oxidation.

ABSTRACT:

Background & aims

The gut-liver axis and hepatic ER-mitochondria miscommunication (at contact sites called MAMs) are involved in the development of metabolic dysfunction-associated steatotic liver disease (MASLD). We investigated the role of circulating aromatic amino acids (AAA) derived from phenylalanine and tyrosine in MASLD potentially through MAM alterations.

Methods

We analyzed AAA metabolomic profiles in individuals with and without MASLD and validated findings in a biopsy-proven cohort. The pro-steatogenic effect of MASLD-associated AAAs was validated in vitro using lipid labeling, MAM structural/functional assays, and palmitate-induced respiration. In vivo effects were tested in mice fed with candidate AAAs, and MAM involvement was confirmed by express

SUBMITTER: Lefebvre R 

PROVIDER: S-EPMC12485909 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature