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Endocrine FGFs: Evolution, Physiology, Pathophysiology, and Pharmacotherapy

Nobuyuki Itoh1, Hiroya Ohta2, Morichika Konishi2

  • 1Medical Innovation Center, Kyoto University Graduate School of Medicine , Kyoto , Japan.

Frontiers in Endocrinology
|October 21, 2015
PubMed

Insights

Endocrine fibroblast growth factors (FGFs), including FGF19, FGF21, and FGF23, are vital signaling molecules that regulate metabolism. These FGFs, along with cofactors Klotho, offer potential diagnostic and therapeutic strategies for metabolic diseases.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Metabolic Research

Background:

  • The fibroblast growth factor (FGF) family has 22 members involved in neuronal functions, development, and metabolism.
  • FGFs act as intracrine, paracrine, or endocrine signaling molecules via FGF receptors (FGFRs).
  • Endocrine FGFs (FGF19, FGF21, FGF23) utilize α-Klotho or β-Klotho cofactors, unlike paracrine FGFs that require heparan sulfate.

Purpose of the Study:

  • To explore the physiological and pathophysiological roles of endocrine FGFs.
  • To highlight the involvement of endocrine FGFs in metabolic diseases.
  • To discuss the diagnostic and therapeutic potential of endocrine FGFs.

Main Methods:

  • Review of existing literature on FGF family, focusing on endocrine FGFs.
  • Analysis of phenotypes from endocrine FGF knockout mice models.
  • Examination of evidence linking endocrine FGFs to human metabolic diseases.

Main Results:

  • Endocrine FGFs regulate bile acid, energy, and phosphate/active vitamin D metabolism.
  • Endocrine FGFs are implicated in the pathophysiology and risk of human metabolic diseases.
  • Endocrine FGFs show promise as biomarkers and therapeutic agents for metabolic disorders.

Conclusions:

  • Endocrine FGFs play critical roles in vertebrate metabolism through a Klotho-dependent signaling system.
  • Further research into endocrine FGFs can lead to novel diagnostic and therapeutic approaches for metabolic diseases.
  • The evolutionary adaptation of endocrine FGFs provides insights into their metabolic functions.
Keywords:
FGFKlothobiomarkerdiseaseendocrinemetabolismmutationpolymorphism

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