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Updated: May 17, 2025

Ileectomy-induced Bile Overaccumulation in Mouse Intestine
Published on: August 21, 2017
Farnesoid X Receptor Regulated Sepsis-Induced Abnormal Bile Acid Metabolism via the Fibroblast Growth Factor
Ziyang Zhou1, Dan Xu1, Liou Huang1
1Trauma-Emergency & Critical Care Medicine Center, Shanghai Fifth People's Hospital Affiliated to Fudan University, Shanghai, China.
Objective:
The study aims to investigate the mechanism of Farnesoid X receptor (FXR) activation in sepsis-induced abnormal bile acid metabolism and the metabolism status of each bile acid type.
Methods:
The sepsis mouse model was developed via lipopolysaccharide intraperitoneal injection and confirmed via hematoxylin and eosin (H&E) staining. FXR agonist activated the FXR/fibroblast growth factor (FGF)15/FGFR pathway via quantitative real-time polymerase chain reaction and Western blot. Consequently, metabolomics and bioinformatics analysis were conducted to identify the alterations in each kind of bile acid content following FXR agonist/inhibitor intervention.
Results:
The H&E staining indicated that FXR activation alleviates the liver injury of the sepsis mouse model. The increased FGF15 and FXFR expression levels and decreased CYP7A1 demonstrated FXR/FGF15/FGFR pathway activation following FXR agonist treatment. Furthermore, total bile acid, interleukin (IL)-6, and tumor necrosis factor-α concentrations were downregulated after FXR activation, whereas IL-10 concentration was upregulated, indicating the alleviated effect of FXR agonist in sepsis. Consequently, metabolomics and bioinformatics analysis determined that T-a-MCA were downregulated in both FXR agonist and inhibitor groups, whereas six bile acid types were altered in the control group.
Conclusion:
FXR activation was crucial in alleviating sepsis-induced hepatic injury and cholestasis through the FGF15/FGFR signaling pathway, and FXR may act as a potential preventive and intervention target of sepsis.
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