title: Regulation of hepatic energy metabolism by the nuclear receptor PXR.
abstract: The pregnane X receptor (PXR) is a nuclear receptor that is traditionally thought to be specialized for sensing xenobiotic exposure. In concurrence with this feature PXR was originally identified to regulate drug-metabolizing enzymes and transporters. During the last ten years it has become clear that PXR harbors broader functions. Evidence obtained both in experimental animals and humans indicate that ligand-activated PXR regulates hepatic glucose and lipid metabolism and affects whole body metabolic homeostasis. Currently, the consequences of PXR activation on overall metabolic health are not yet fully understood and varying results on the effect of PXR activation or knockout on metabolic disorders and weight gain have been published in mouse models. Rifampicin and St. John's wort, the prototypical human PXR agonists, impair glucose tolerance in healthy volunteers. Chronic exposure to PXR agonists could potentially represent a risk factor for diabetes and metabolic syndrome. This article is part of a Special Issue entitled: Xenobiotic nuclear receptors: New Tricks for An Old Dog, edited by Dr. Wen Xie.
authors.affiliation: Research Unit of Biomedicine, Pharmacology and Toxicology, University of Oulu, Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland. Electronic address: jukka.hakkola@oulu.fi.
authors.forename: Jukka
authors.initials: J
authors.lastname: Hakkola
authors.affiliation: School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: Jaana
authors.initials: J
authors.lastname: Rysä
authors.affiliation: Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland; Research Unit of Internal Medicine, University of Oulu, Oulu, Finland; Department of Internal Medicine, Oulu University Hospital, Oulu, Finland; Biocenter Oulu, Oulu, Finland.
authors.forename: Janne
authors.initials: J
authors.lastname: Hukkanen
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D005943:Gluconeogenesis / Q000235:genetics; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects / Q000235:genetics; D006801:Humans; D020902:Hypericum / Q000009:adverse effects / Q000737:chemistry; D008658:Inactivation, Metabolic / Q000235:genetics*; D050155:Lipogenesis / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D024821:Metabolic Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism*; D012293:Rifampin / Q000009:adverse effects; D015398:Signal Transduction
chemical_list: D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; D005947:Glucose; D012293:Rifampin
keywords: Diabetes; Glucose; Lipid; Liver; Metabolic syndrome; PXR