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Fibroblast growth factor 21: from pharmacology to physiology

Steven A Kliewer1, David J Mangelsdorf

  • 1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 73590-9041, USA. steven.kliewer@utsouthwestern.edu

The American Journal of Clinical Nutrition
|November 13, 2009
PubMed

Insights

Fibroblast growth factor 21 (FGF21) is an endocrine hormone with significant metabolic actions. It enhances insulin sensitivity, reduces triglycerides, and promotes weight loss, playing a key role in the body's starvation response.

Area of Science:

  • Endocrinology
  • Metabolic Regulation
  • Molecular Biology

Background:

  • Fibroblast growth factor 21 (FGF21) is an atypical endocrine hormone within the FGF family.
  • Pharmacologic studies indicate FGF21 possesses broad metabolic effects in obese animals, including improved insulin sensitivity, reduced triglycerides, and weight loss.

Purpose of the Study:

  • To highlight recent advances in understanding the pharmacologic and physiologic actions of FGF21.
  • To elucidate FGF21's role in metabolic regulation during fasting and fed states.

Main Methods:

  • Review of pharmacologic studies on FGF21's metabolic effects in rodents and primates.
  • Analysis of FGF21 induction mechanisms during fasting in lean rodents involving PPARα.
  • Investigation of FGF21's role in hepatic gluconeogenesis, fatty acid oxidation, and ketogenesis.

Main Results:

  • FGF21 expression is induced by prolonged fasting in the liver via peroxisome proliferator-activated receptor alpha (PPARα).
  • FGF21 stimulates hepatic gluconeogenesis, fatty acid oxidation, and ketogenesis, while also inducing PGC-1α.
  • FGF21 expression in adipose tissue is induced by peroxisome proliferator-activated receptor gamma (PPARγ), suggesting a role in fed-state metabolism.

Conclusions:

  • FGF21 is a critical regulator of the adaptive starvation response, coordinating metabolic adjustments.
  • FGF21 exhibits significant therapeutic potential for metabolic disorders like obesity and insulin resistance.
  • Further research into FGF21's dual role in fasting and fed states is warranted.

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