Stress-induced FGF21 and GDF15 in obesity and obesity resistance

Trends Endocrinol Metab. 2021 Nov;32(11):904-915. doi: 10.1016/j.tem.2021.08.008. Epub 2021 Sep 13.

Abstract

Fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) are established as stress-responsive cytokines that can modulate energy balance by increasing energy expenditure or suppressing food intake, respectively. Despite their pharmacologically induced beneficial effects on obesity and comorbidities, circulating levels of both cytokines are elevated during obesity and related metabolic complications. On the other hand, endocrine crosstalk via FGF21 and GDF15 was also reported to play a crucial role in genetically modified mouse models of mitochondrial perturbations leading to diet-induced obesity (DIO) resistance. This review aims to dissect the complexities of endogenous FGF21 and GDF15 action in obesity versus DIO resistance for the regulation of energy balance in metabolic health and disease.

Keywords: FGF21; GDF15; adipose tissue; energy balance; mitochondrial integrated stress response; muscle; obesity resistance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Energy Metabolism / physiology
  • Fibroblast Growth Factors* / genetics
  • Fibroblast Growth Factors* / metabolism
  • Growth Differentiation Factor 15 / genetics
  • Growth Differentiation Factor 15 / metabolism*
  • Humans
  • Mice
  • Obesity / metabolism
  • Stress, Physiological

Substances

  • GDF15 protein, human
  • Gdf15 protein, mouse
  • Growth Differentiation Factor 15
  • fibroblast growth factor 21
  • Fibroblast Growth Factors