Choline attenuates NEFA-induced hepatic steatosis via GNMT regulation in hepatocytes.

ABSTRACT: To elucidate the molecular mechanisms by which choline regulates hepatic lipid metabolism under negative energy balance conditions, we established non-esterified fatty acid (NEFA)-induced hepatic steatosis models in both calf primary hepatocytes and human LO2 hepatocytes. Choline supplementation significantly reduced intracellular triglyceride accumulation and cytotoxicity induced by NEFA exposure. Transcriptomic profiling identified glycine N-methyltransferase (GNMT) as a key differentially expressed gene. Subsequent experiments confirmed that choline upregulated GNMT expression at both the mRNA and protein levels in a concentration-dependent manner. Knockdown of GNMT reversed the beneficial effects of choline on genes related to lipid synthesis (FAS, ACC), fatty acid oxidation (CPT1), li

SUBMITTER: Du X 

PROVIDER: S-EPMC12615869 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature