FGF1 ameliorates hepatic steatosis through acute activation of the unfolded protein response and VLDL production.

ABSTRACT:

Background & aims

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a serious chronic liver disease with limited therapeutic options. Fibroblast growth factor (FGF) analogs show promising therapeutic benefits for MASLD, yet the underlying mechanisms remain incompletely understood. Here, we studied the mechanism underlying the anti-steatotic properties of FGF1, the prototype member of the FGF family.

Methods

The effect of FGF1 was studied in human and rodent hepatocytes and in obese mouse models exhibiting acute or chronic endoplasmic reticulum (ER) stress characteristic of MASLD. Metabolic analysis and proteomics were applied to evaluate liver physiology, ER stress and signaling.

Results

We show that FGF1 reduces hepatic triglyceride (TG) levels in o

SUBMITTER: van Zutphen T 

PROVIDER: S-EPMC12800356 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature