Fibroblast growth factor (FGF)-21 based therapies: A magic bullet for nonalcoholic fatty liver disease (NAFLD)?

Area of Science:

• Endocrinology
• Metabolic Diseases
• Hepatology

Background:

• Fibroblast growth factor (FGF) 21 is a signaling molecule with paracrine/autocrine and endocrine functions.
• FGF21 specificity is mediated by β-Klotho co-receptor, primarily in hepatic and adipose tissues.
• The FGF21/FGFR/β-Klotho pathway influences fat and glucose metabolism.

Purpose of the Study:

• To review preclinical and clinical data on FGF21 agonist therapies for nonalcoholic fatty liver disease (NAFLD).
• To assess the efficacy and safety of FGF21 agonist treatments in development for NAFLD.

Main Methods:

• Summary of preclinical study findings.
• Analysis of clinical trial data for FGF21 agonist therapies.
• Evaluation of safety profiles, including adverse events.

Main Results:

• Preclinical data suggest FGF21 pathway targeting may reverse hepatic fat infiltration, inflammation, and fibrosis.
• Clinical data indicate potential efficacy of FGF21 agonist therapies in NAFLD patients.
• Identified safety concerns include injection site reactions and potential effects on bone homeostasis.

Conclusions:

• FGF21 agonist therapies represent a promising avenue for NAFLD treatment.
• Further investigation and careful safety evaluation are warranted before widespread clinical adoption.
• Targeting the FGF21/FGFR/β-Klotho pathway holds potential for managing NAFLD.