Double knockout of FFAR4 and FGF21 aggravates metabolic disorders in mice

Int J Biol Macromol. 2023 Dec 31;253(Pt 1):126553. doi: 10.1016/j.ijbiomac.2023.126553. Epub 2023 Aug 30.

Abstract

Several investigations have examined the involvement of free fatty acid receptor 4 (FFAR4) in metabolic disorders, but its action remains controversial. To investigate whether endogenous fibroblast growth factor 21 (FGF21)-mediated signaling controls the metabolic status in FFAR4-deficient mice, we generated FFAR4/FGF21 double knockout (DKO) mice. We also evaluated the role of FGF21 on glucose and lipid metabolism in FFAR4 KO mice fed a high-fat diet. Levels of FGF21 were significantly increased in FFAR4-deficient mice and double deletion of FGF21 and FFAR4 led to severe metabolic disorders. Additionally, FFAR4/FGF21 DKO mice displayed metabolic abnormalities that may be caused by decreased energy expenditure. Collectively, this study characterized the effects of endogenous FGF21, which acts as a master feedback regulator in the absence of FFAR4.

Keywords: Diabetes; FFAR4; FGF21; Metabolic disorders; NAFLD; Obesity.

MeSH terms

  • Animals
  • Diet, High-Fat / adverse effects
  • Energy Metabolism / genetics
  • Fibroblast Growth Factors* / genetics
  • Fibroblast Growth Factors* / metabolism
  • Glucose / metabolism
  • Liver / metabolism
  • Metabolic Diseases* / genetics
  • Metabolic Diseases* / metabolism
  • Mice
  • Mice, Inbred C57BL

Substances

  • fibroblast growth factor 21
  • Fibroblast Growth Factors
  • Glucose