Xenoreceptors CAR and PXR activation and consequences on lipid metabolism, glucose homeostasis, and inflammatory response.
Xenobiotic and drug metabolism and transport are managed by a large number of genes coordinately regulated by at least three nuclear receptors or xenosensors: aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR, NR1I3), and pregnane X receptor (PXR, NR1I2). Initially characterized as xenosensors, it is now evident that CAR and PXR also trigger pleiotropic effects on liver function. Recent studies have shown the existence of crosstalk between xenosensors and other nuclear receptors or transcription factors controlling endogenous signaling pathways which regulate physiological functions. This review is focused on recent observations showing that activation of CAR and PXR alters lipid metabolism, glucose homeostasis, and inflammation by interfering with HNF4alpha, FoxO1, FoxA2, PGC1alpha, or NFkB p65. Such crosstalks explain clinical observations and provide molecular mechanisms allowing understanding how xenobiotics and drugs may affect physiological functions and provoke endocrine disruptions.
Moreau
Amélie
A
Inserm, UMR-U632, 1919 route de Mende, F-34293 Montpellier, France.
Vilarem
Marie José
MJ
Maurel
Patrick
P
Pascussi
Jean Marc
JM
D000818:Animals; D000090702:Constitutive Androstane Receptor; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D050356:Lipid Metabolism; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology; D014157:Transcription Factors / Q000378:metabolism*
D000090702:Constitutive Androstane Receptor; C000625852:NR1I2 protein, human; C000716327:NR1I3 protein, human; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; D005947:Glucose