Nuclear Receptor Metabolism of Bile Acids and Xenobiotics: A Coordinated Detoxification System with Impact on Health and Diseases

• Published in: International journal of molecular sciences Vol. 19; no. 11; p. 3630
• Main Authors: Garcia, Manon, Thirouard, Laura, Sedès, Lauriane, Monrose, Mélusine, Holota, Hélène, Caira, Françoise, Volle, David H, Beaudoin, Claude
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 17.11.2018; MDPI
• Subjects: Bile; Bile acids; Cancer; CAR; Cholesterol; Detoxification; drug resistance; Endocrinology and metabolism; Enzymes; FXR; Gallbladder; Gene expression; Homeostasis; Human health and pathology; Life Sciences; Ligands; Liver; Metabolism; metabolism and transport; Metabolites; Nuclear receptors; Proteins; PXR; Review; Sensors; Small intestine; Sterols; Structure-function relationships; Transcription; Xenobiotics; FXR; CAR; bile acids; xenobiotics; cancer; PXR; drug resistance; metabolism and transport
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19113630

Structural and functional studies have provided numerous insights over the past years on how members of the nuclear hormone receptor superfamily tightly regulate the expression of drug-metabolizing enzymes and transporters. Besides the role of the farnesoid X receptor (FXR) in the transcriptional control of bile acid transport and metabolism, this review provides an overview on how this metabolic sensor prevents the accumulation of toxic byproducts derived from endogenous metabolites, as well as of exogenous chemicals, in coordination with the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR). Decrypting this network should provide cues to better understand how these metabolic nuclear receptors participate in physiologic and pathologic processes with potential validation as therapeutic targets in human disabilities and cancers.