1. Academic Validation
  2. Double knockout of FFAR4 and FGF21 aggravates metabolic disorders in mice

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

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: shenglongzhu@jiangnan.edu.cn.
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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