Role of bile acids and bile acid receptors in metabolic regulation.

@article{Lefebvre2009RoleOB,
  title={Role of bile acids and bile acid receptors in metabolic regulation.},
  author={Philippe Lefebvre and Bertrand Cariou and Fleur Lien and Folkert Kuipers and Bart Staels},
  journal={Physiological reviews},
  year={2009},
  volume={89 1},
  pages={
          147-91
        }
}
The incidence of the metabolic syndrome has taken epidemic proportions in the past decades, contributing to an increased risk of cardiovascular disease and diabetes. The metabolic syndrome can be defined as a cluster of cardiovascular disease risk factors including visceral obesity, insulin resistance, dyslipidemia, increased blood pressure, and hypercoagulability. The farnesoid X receptor (FXR) belongs to the superfamily of ligand-activated nuclear receptor transcription factors. FXR is… 
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381 References

Glucose regulates the expression of the farnesoid X receptor in liver.

It is demonstrated that FXR is decreased in animal models of diabetes and regulated by glucose likely via the pentose phosphate pathway, and expression of the FXR target genes, SHP and apolipoprotein C-III, were additively regulated by D-glucose and FXR ligands.

Farnesoid X receptor is essential for normal glucose homeostasis.

A link between lipid and glucose metabolism mediated by the FXR-SHP cascade is identified, and bile acid activation of FXR in WT mice repressed expression of gluconeogenic genes and decreased serum glucose.

Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation

It is shown that the administration of BAs to mice increases energy expenditure in brown adipose tissue, preventing obesity and resistance to insulin, and indicates that BAs might be able to function beyond the control of BA homeostasis as general metabolic integrators.

Farnesoid X receptor: a new player in glucose metabolism?

The authors found that FXR activation by bile acids or synthetic FXR-specific agonists led to an increased expression of the phosphoenolpyruvate carboxykinase (PEPCK) gene in vitro in rat and human hepatocytes, as well as in vivo in mouse liver.

Farnesoid X Receptor Modulates Renal Lipid Metabolism, Fibrosis, and Diabetic Nephropathy

OBJECTIVE—Recent studies indicate an important role for nuclear receptors in regulating lipid and carbohydrate metabolism, fibrosis, and inflammation. Farnesoid X receptor (FXR) is a member of the…

The Farnesoid X Receptor Modulates Adiposity and Peripheral Insulin Sensitivity in Mice*

A novel role of FXR in the regulation of peripheral insulin sensitivity and adipocyte function is identified, which opens new perspectives for the treatment of type 2 diabetes.

Activation of the farnesoid X receptor improves lipid metabolism in combined hyperlipidemic hamsters.

It is demonstrated that activation of FXR with CDCA effectively lowers plasma triglyceride and cholesterol concentrations, mainly by decreasing de novo lipogenesis and hepatic secretion of triglyceride-rich lipoproteins.

The Farnesoid X Receptor Modulates Hepatic Carbohydrate Metabolism during the Fasting-Refeeding Transition*

A novel role for FXR is identified as a modulator of hepatic carbohydrate metabolism by identifying an accelerated response to high carbohydrate refeeding with an accelerated induction of glycolytic and lipogenic genes and a more pronounced repression of gluconeogenic genes.

Bile acid-activated nuclear receptor FXR suppresses apolipoprotein A-I transcription via a negative FXR response element.

Bile acids that are activators of the nuclear receptor farnesoid X receptor (FXR) as negative regulators of human apoA-I expression are identified and promoter mutation analysis and gel-shift experiments in HepG2 cells demonstrated that bile acid-activated FXR decreases human apos A-I promoter activity by a negative FXR response element mapped to the C site.

A common polymorphism in the bile acid receptor farnesoid X receptor is associated with decreased hepatic target gene expression.

These findings are the first to identify the presence of a common genetic variant in FXR with functional consequences that could contribute to disease risk or therapeutic outcomes.
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