Double knockout of FFAR4 and FGF21 aggravates metabolic disorders in mice

  • Int J Biol Macromol. 2023 Aug 30;126553. doi: 10.1016/j.ijbiomac.2023.126553.
Lengyun Wei  1 ,  Xianlong Ye  2 ,  Siyuan Cui  3 ,  Dashuai Li  4 ,  Shenglong Zhu  5
Affiliations
  • 1. School of Life Science, Anhui Medical University, Hefei 230032, China; Wuxi School of Medicine, Jiangnan University, Wuxi, China.
  • 2. Ganjiang Chinese Medicine Innovation Center, Nanchang 330000, China.
  • 3. Jiangnan University Medical Center, Wuxi, China.
  • 4. School of Life Science, Anhui Medical University, Hefei 230032, China.
  • 5. Jiangnan University Medical Center, Wuxi, China; Wuxi School of Medicine, Jiangnan University, Wuxi, China. Electronic address: [email protected].
PMID: 37657572 DOI: 10.1016/j.ijbiomac.2023.126553
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.
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