Metformin stimulates FGF21 expression in primary hepatocytes

Area of Science:

• Metabolic regulation
• Hepatocyte function
• Endocrinology

Background:

• Fibroblast growth factor 21 (FGF21) is a key metabolic regulator.
• The precise mechanisms controlling FGF21 expression remain incompletely understood.
• Metabolic state influences FGF21 regulation, prompting investigation into drug effects.

Purpose of the Study:

• To investigate if metformin, an indirect AMPK activator, influences FGF21 expression in hepatocytes.
• To elucidate the role of AMP-activated protein kinase (AMPK) in metformin-induced FGF21 regulation.

Main Methods:

• Primary rat and human hepatocytes were cultured and treated with metformin.
• FGF21 mRNA and protein levels were quantified.
• The AMPK inhibitor Compound C was used to assess AMPK's involvement.

Main Results:

• Metformin treatment resulted in a significant, dose-dependent increase in FGF21 expression in both rat and human hepatocytes.
• The observed increase in FGF21 by metformin was abrogated by the AMPK inhibitor Compound C.
• These findings indicate metformin is a potent inducer of hepatic FGF21.

Conclusions:

• Metformin stimulates hepatic FGF21 expression, with the effect mediated via AMPK activation.
• The induction of FGF21 by metformin may be a crucial mechanism underlying its anti-diabetic efficacy.
• Further research into FGF21's role in glucose homeostasis is warranted.