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Updated: Jul 17, 2025
Body Composition and Metabolic Caging Analysis in High Fat Fed Mice
Published on: May 24, 2018
Double knockout of FFAR4 and FGF21 aggravates metabolic disorders in mice
Lengyun Wei1, Xianlong Ye2, Siyuan Cui3
1School of Life Science, Anhui Medical University, Hefei 230032, China; Wuxi School of Medicine, Jiangnan University, Wuxi, China.
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.
Insights
Fibroblast growth factor 21 (FGF21) signaling is crucial for metabolic health, especially when free fatty acid receptor 4 (FFAR4) is absent. Deleting both FGF21 and FFAR4 causes severe metabolic disorders, highlighting FGF21's feedback role.
Area of Science:
- Metabolic disorders
- Endocrinology
- Molecular biology
Background:
- Free fatty acid receptor 4 (FFAR4) involvement in metabolic disorders is debated.
- Endogenous fibroblast growth factor 21 (FGF21) signaling's role in FFAR4-deficient mice requires clarification.
Purpose of the Study:
- To investigate the role of endogenous FGF21 signaling in FFAR4-deficient mice.
- To determine the impact of FFAR4 and FGF21 double deficiency on metabolic status.
Main Methods:
- Generation of FFAR4/FGF21 double knockout (DKO) mice.
- Evaluation of glucose and lipid metabolism in FFAR4 KO mice on a high-fat diet.
Main Results:
- FGF21 levels were significantly elevated in FFAR4-deficient mice.
- Double deletion of FGF21 and FFAR4 resulted in severe metabolic disorders.
- FFAR4/FGF21 DKO mice exhibited metabolic abnormalities linked to reduced energy expenditure.
Conclusions:
- Endogenous FGF21 acts as a master feedback regulator in the absence of FFAR4.
- FFAR4 deficiency influences FGF21 levels and metabolic regulation.
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