PNPLA3 I148M variant links to adverse metabolic traits in MASLD during fasting and feeding.

ABSTRACT:

Background & aims

The PNPLA3 rs738409 polymorphism is the most abundant genetic risk factor associated with progression of metabolic dysfunction-associated steatotic liver disease (MASLD) to steatohepatitis (MASH) and fibrosis. Although fasting and feeding affect PNPLA3 expression, molecular insights into the pathophysiological influence remain scarce.

Methods

We analyzed 353 serum samples of patients with MASLD from two German tertiary centers using nuclear magnetic resonance (NMR)-proteometabolomics. Patients were stratified by PNPLA3 rs738409 C>G genotype: 'CC', 'CG', and 'GG'. Metabolites, lipoproteins, and glycoproteins were assessed based on fasting status.

Results

PNPLA3 GG displayed a distinct metabolic profile, with notable alterat

SUBMITTER: Jegodzinski L 

PROVIDER: S-EPMC12269597 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature