The farnesoid X receptor (FXR) is implicated in cholesterol and bile acid homeostasis; however, its role following myocardial infarction (MI) has yet to be elucidated. The aim of the present study was to investigate the effects of FXR knockout on left ventricular (LV) remodeling following MI. Coronary arteries of wild type (WT) and FXR‑/‑ mice were permanently occluded to cause MI, and serial e...

Farnesoid X receptor (FXR) plays a pivotal role in the regulation of various metabolic pathways as well as liver regeneration. However, the casual link between cell proliferative effects during liver regeneration and metabolic regulation of FXR was elusive. In this study, we found that FXR activation significantly promotes HepG2 cell proliferation accompanied with metabolic switch towards the e...

We investigated how cholesterol feeding regulates cholesterol 7alpha-hydroxylase (CYP7A1) via the nuclear receptors farnesoid X receptor (FXR) and liver X receptor alpha (LXRalpha) in New Zealand white rabbits. After 1 day of 2% cholesterol feeding, when the bile acid pool size had not expanded, mRNA levels of the FXR target genes short-heterodimer partner (SHP) and sterol 12alpha-hydroxylase (...

Type 2 diabetes mellitus is associated with alterations in bile acid (BA) signaling. The aim of our study was to test whether pancreatic β-cells contribute to BA-dependent regulation of glucose homeostasis. Experiments were performed with islets from wild-type, farnesoid X receptor (FXR) knockout (KO), and β-cell ATP-dependent K(+) (K(ATP)) channel gene SUR1 (ABCC8) KO mice, respectively. Sodiu...

The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily that functions as an endogenous sensor for bile acids and regulates cholesterol and fatty acid metabolism. The effect of FXR activation on aortic plaque formation was assessed by feeding apolipoprotein E-deficient (ApoE-/-) mice with the synthetic FXR ligand INT-747, a cheno-deoxycholic acid derivative, at doses of 3...

Farnesoid X receptor (FXR) is a bile acid nuclear receptor described through mouse knockout studies as a tumor suppressor for the development of colon adenocarcinomas. This study investigates the regulation of FXR in the development of human colon cancer. We used immunohistochemistry of FXR in normal tissue (n = 238), polyps (n = 32), and adenocarcinomas, staged I-IV (n = 43, 39, 68, and 9), of...

Farnesoid X receptor (FXR), the primary bile acid-sensing nuclear receptor, also is known for its anticancer properties. It is known that FXR deficiency in mice results in spontaneous hepatocellular carcinoma (HCC), but the mechanisms are not completely understood. We report that sustained activation of the Wnt/β-catenin pathway is associated with spontaneous HCC in FXR-knockout (KO) mice. HCC ...

The farnesoid X receptor (FXR) is a bile acid-regulated nuclear receptor expressed in enterohepatic tissues. In this study we investigated whether FXR is expressed by cells of innate immunity and regulates inflammation in animal models of colitis. Acute (7 days) and chronic (8 wk) colitis were induced in wild-type and FXR(-/-) mice by intrarectal administration of trinitrobenzensulfonic acid or...

Bile acids have been considered intestinal tumor promoters, and because they are natural ligands for the nuclear receptor FXR, we examined the role of FXR in intestinal tumorigenesis. Using gain- and loss-of-function studies, we found that FXR suppresses intestinal tumorigenesis in vivo. Loss of FXR in the ApcMin/+ and in the chronic colitis mouse models of intestinal tumorigenesis resulted in ...

Glucose-dependent organs such as the brain are sustained through periods of fasting by glucose production in the liver, called hepatic gluconeogenesis. Normally, rising blood glucose levels homeostatically suppress gluconeogenesis. In obesity-related type 2 diabetes, however, insulin resistance and elevated glucagon inhibit the suppression of gluconeogenesis, contributing to hyperglycemia. Ther...