The nuclear receptors farnesoid X receptor (FXR; NR1H4) and small heterodimer partner (SHP; NR0B2) play crucial roles in bile acid homeostasis. Global double knockout of FXR and SHP signaling (DKO) causes severe cholestasis and liver injury at early ages.

Jan 1, 2021 · The importance of FXR in the enterohepatic circulation of bile acids. FXR represses the transcriptional activity of hepatic Cyp7a1 and Cyp8b1 by upregulating the expression of SHP. FXR stimulates the synthesis of the FGF-15/19-FGFR4 pathways to …

Apr 15, 2025 · Since Fxr is a key nuclear receptor controlling BA homeostasis, we examined the expression of Fxr and its transcriptional targets, Shp and Bsep. While Fxr expression was unchanged, Fxr ...

Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are key regulators of metabolism. Here, we report a previously unknown function for the hepatic FXR-SHP axis in controlling protein N-linked glycosylation.

Jul 1, 2021 · FXR reduces the major transcription factor for lipogenic pathways, SREBP-1c via induction of SHP and thereby reduces fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC) and sterol CoA desaturase (SCD1) [64], although SHP independent repression appears to …

Still, most FXR/RXRα target genes are maximally expressed in the presence of both ligands, including the small heterodimer partner (SHP). Here, we revisited the FXR/RXRα-mediated regulation of human SHP.

These results suggest that strategies aimed at increasing FXR activity and the repressive effects of SHP should be explored to correct hypertriglyceridemia. We explored the effects of bile acids on triglyceride (TG) homeostasis using a combination of molecular, cellular, and animal models.

Sep 1, 2000 · Through the use of a potent, nonsteroidal FXR ligand, we have identified SHP-1 as an FXR target gene in the liver of humans and rodents. Furthermore, we have demonstrated that SHP-1 can interact with LRH-1 and efficiently repress expression of CYP7A1.

FXR-SHP通路是肝脏调节胆汁代谢的关键通路。 FXR通过结合SHP基因启动子区域的FXR结合位点(FXR Response Element, FXRRE),又称IR1序列,以调控SHP基因的转录表达，进而维持肝脏胆汁合成与代谢稳态。作为FXR最主要的下游基因，SHP与肝脏肿瘤形成关系密切。

Combined deletion of the hepatic FXR/SHP axis improves glucose/fatty acid homeostasis in aged mice, reversing the aging phenotype of body weight gain, increased adiposity, and glucose/insulin tolerance, suggesting a central role of this axis in whole-body energy homeostasis.