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Fibroblast growth factor 21: A "rheostat" for metabolic regulation?

Qin-Ying She1, Jing-Fu Bao2, Hui-Zhen Wang2

  • 1Department of Endocrinology, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou 510999, China; Department of Nephrology, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou 510999, China.

Metabolism: Clinical and Experimental
|February 20, 2022
PubMed

Insights

Fibroblast growth factor 21 (FGF21) helps maintain metabolic balance by regulating nutrient fluctuations. Its therapeutic potential for metabolic disorders needs further investigation due to variable clinical trial outcomes.

Area of Science:

  • Endocrinology
  • Metabolic Regulation
  • Nutritional Science

Background:

  • Fibroblast growth factor 21 (FGF21) is a key regulator of metabolic homeostasis, with significant research over two decades elucidating its roles.
  • FGF21's potential as a therapeutic agent for metabolic disorders has been explored, yet clinical trial results have been inconsistent.
  • FGF21 is influenced by nutrient intake and released by the liver and adipose tissue, impacting appetite and energy metabolism.

Purpose of the Study:

  • To re-evaluate the role of FGF21 beyond simple anti-diabetic or anti-obesity effects.
  • To propose a revised understanding of FGF21 as a nutrient-balancing factor crucial for energy supply.
  • To highlight the context-dependent nature of FGF21's functions in glycometabolism and lipometabolism.

Main Methods:

  • Review and synthesis of existing research on FGF21's physiological roles and clinical trial data.
  • Analysis of FGF21's regulatory pathways involving nutrient sensing and hormonal signaling.
  • Comparative assessment of FGF21's effects across different metabolic states.

Main Results:

  • FGF21 dynamically responds to nutrient availability and influences central and peripheral metabolic tissues.
  • Evidence suggests FGF21's primary function is to balance nutrient fluctuations for energy homeostasis.
  • Clinical efficacy of FGF21 appears contingent on the specific metabolic context, explaining variable trial outcomes.

Conclusions:

  • FGF21 should be viewed as a critical mediator of nutrient balance rather than solely an anti-obesity or anti-hyperglycemia agent.
  • The pharmacological application of FGF21 requires careful consideration of the patient's metabolic state.
  • Further research is needed to optimize FGF21-based therapies by accounting for its context-dependent actions.
Keywords:
Diabetes milieusFibroblast growth factor-21MetabolismObesityβ-Klotho

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