FGF21 ameliorates nonalcoholic fatty liver disease by inducing autophagy

Area of Science:

• Metabolic disease research
• Cellular biology
• Molecular medicine

Background:

• Nonalcoholic fatty liver disease (NAFLD) is a growing global health concern.
• Fibroblast growth factor 21 (FGF21) is a potential therapeutic target for metabolic disorders.
• The precise mechanism of FGF21's action in NAFLD, particularly its link to autophagy, requires further elucidation.

Purpose of the Study:

• To investigate the therapeutic role of fibroblast growth factor 21 (FGF21) in nonalcoholic fatty liver disease (NAFLD).
• To determine if FGF21 exerts its beneficial effects in NAFLD by inducing autophagy.

Main Methods:

• Monosodium L-glutamate (MSG)-induced obese mice and normal lean mice were treated with vehicle, Fenofibrate, or recombinant murine FGF21.
• Metabolic parameters, including body weight, blood glucose, and lipid levels, were analyzed.
• Hepatic and fat gene expression, protein levels related to autophagy (e.g., LC3, Beclin-1, ATG5), and autophagic flux were assessed in vivo and in vitro using HepG2 cells.

Main Results:

• FGF21 treatment significantly reduced body weight and serum triglyceride levels in MSG-induced obese mice.
• FGF21 improved insulin sensitivity and reversed hepatic steatosis in the NAFLD mouse model.
• FGF21 upregulated autophagy-related proteins and increased autophagosome formation in both mice and HepG2 cells, enhancing autophagic flux.

Conclusions:

• Fibroblast growth factor 21 (FGF21) demonstrates significant therapeutic potential for nonalcoholic fatty liver disease (NAFLD).
• FGF21 corrects key metabolic dysfunctions associated with NAFLD through the induction of autophagy.
• These findings highlight FGF21 as a promising therapeutic agent for NAFLD, acting via the autophagy pathway.