Dataset Information

HNF4α contributes to hepatic CAR dysfunction in polymicrobial sepsis

ABSTRACT: Constitutive androstane receptor (CAR) is a xenobiotic nuclear receptor mainly expressed in the liver, where it regulates drug metabolism and energy homeostasis. CAR has emerged as a promising therapeutic target for diabetes, fatty liver disease, and alcoholic liver disease, but it has not been investigated in the context of sepsis. Here, we show that sepsis impairs CAR function in the liver, partly due to reduced transcription mediated by HNF4α, the key liver identity transcription factor, and partly due to decreased DNA binding, caused by chromatin remodeling, also mediated by HNF4α. This impairment leads to the downregulation of several genes and proteins involved in monocarboxylic acid, fatty acid, and xenobiotic metabolism, contributing to increased sepsis lethality, and is associated with an elevated hepatic acute phase response. LC-MSMS analysis was used to identify the proteins differentially expressed in the liver 24h after sepsis onset.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver

SUBMITTER: Sara Dufour

LAB HEAD: Claude Libert

PROVIDER: PXD062961 | Pride | 2025-09-15

REPOSITORIES: Pride

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			Action	DRS
	Experimental_design_forPRIDE.xlsx	Xlsx
	PRC-6559DIA_UPRC_10090_H0908_2p_IonOpt18_25cm_PRC-6559_Libert-DIA-1_rerrun_20241205105758.raw	Raw
	PRC-6559DIA_UPRC_10090_H0910_2p_IonOpt18_25cm_PRC-6559_Libert-DIA-2.raw	Raw
	PRC-6559DIA_UPRC_10090_H0912_2p_IonOpt18_25cm_PRC-6559_Libert-DIA-3.raw	Raw
	PRC-6559DIA_UPRC_10090_H0914_2p_IonOpt18_25cm_PRC-6559_Libert-DIA-4.raw	Raw

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HNF4α contributes to hepatic CAR dysfunction in polymicrobial sepsis.

Van Dender Céline C Timmermans Steven S Roes Maxime M Hellemans Madeleine M Moens Elise E Nuyttens Louise L Claes Maarten M Roman Bart B De Bosscher Karolien K Vandewalle Jolien J Libert Claude C

Frontiers in immunology 20250819

The constitutive androstane receptor (CAR), encoded by the <i>Nr1i3</i> gene, is a nuclear receptor mainly expressed in the liver, where it regulates (xenobiotic) drug and bile acid metabolism, bilirubin clearance and energy homeostasis. CAR has emerged as a promising therapeutic target for diabetes, fatty liver disease and alcoholic liver disease, but it has barely been investigated in the context of sepsis. Since alterations in drug metabolism have been observed in sepsis patients, who may als ...[more]

PMID: 40904458

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