Fibroblast Growth Factor 15/19: From Basic Functions to Therapeutic Perspectives.

Area of Science:

• Endocrinology and Metabolism
• Developmental Biology
• Hepatology

Background:

• Fibroblast growth factor (FGF)15/19 represents a unique subfamily of FGFs functioning as hormones.
• Initially recognized for roles in fetal organogenesis, FGF15/19 is crucial for adult metabolic regulation, particularly bile acid synthesis and nutrient partitioning.
• Therapeutic application of FGF19 has been hindered by challenges in activating hepatocyte proliferation.

Purpose of the Study:

• To review the fundamental knowledge of FGF15/19 in both mice and humans.
• To highlight differences in regulation, structure, signaling, and biological properties between murine FGF15 and human FGF19.
• To discuss the therapeutic potential and implications of FGF19 for human diseases.

Main Methods:

• Literature review focusing on FGF15/19 research.
• Comparative analysis of FGF15 (murine) and FGF19 (human) biology.
• Examination of therapeutic strategies and outcomes.

Main Results:

• FGF15/19 plays significant roles in organogenesis and adult metabolic homeostasis.
• Pharmacological FGF19 exhibits antiobesity and antidiabetic effects in rodents, partly mediated by the brain.
• Genetic reengineering has overcome previous limitations in FGF19's ability to activate hepatocyte proliferation.

Conclusions:

• Understanding the species-specific differences between FGF15 and FGF19 is critical for clinical translation.
• FGF19 holds therapeutic promise for metabolic disorders, liver diseases, and cancer.
• Further research is needed to fully elucidate FGF15/19's complex roles and optimize its therapeutic use.