Constitutive androstane receptor activation by 2,4,6-triphenyldioxane-1,3 suppresses the expression of the gluconeogenic genes

Protein arginine methyltransferase 5 (PRMT5) is a novel coactivator of constitutive androstane receptor (CAR)

“…PRMT5 was recently reported to enhance gluconeogenic gene expression via histone H3R2 methylation [30]. It is known that CAR represses the expression of gluconeogenic genes, such as G6Pase and PEPCK [31,32]. We speculate that CAR-mediated repression of guluconeogenesis might be partly due to the down-regulation of PRMT5.…”

Xenosensor CAR mediates down-regulation of miR-122 and up-regulation of miR-122 targets in the liver

“…Additionally, it was shown that the overexpression of HNF4α in rodent HCC models blocks carcinogenesis and metastasis (Yin et al, 2008;Ning et al, 2010). In previous studies, we and others have shown that CAR diminished the association of HNF4α with its specific binding site in gene promoters (Miao et al, 2006;Kachaylo et al, 2012;Yarushkin et al, 2013). Similar to these previous studies, we demonstrated that TCPOBOP, direct agonist of CAR, produced a significant decrease in the level of miR-122, a HNF4α target, by competing with HNF4α for binding to the DR1 motif in pri-miR-122 promoter.…”

“…CAR is also able to bind to DR3 and everted repeat (ER) 6 elements in promoters (Goodwin et al, 2002). Moreover, activated CAR can repress gene expression by competing with HNF4α to bind to the DR1 motif (Miao et al, 2006;Kachaylo et al, 2012;Yarushkin et al, 2013). As HNF4α is the most important transcription regulator of miR-122 levels, in the present study we investigated HNF4α-CAR crosstalk in the regulation of miR-122 and its targets in mouse livers.…”

“…Moreover, CAR regulates other physiologically important enzymes in the liver. For instance, CAR has been demonstrated not only to be a xenosensor but also to play a role in endogenous energy metabolism (Ueda et al, 2002;Kachaylo et al, 2012;Yarushkin et al, 2013). CAR activation by xenobiotics also causes liver hyperplasia in the short term Blanco-Bose et al, 2008).…”

Enteric Microbiota–Gut–Brain Axis from the Perspective of Nuclear Receptors

“…Long-term CAR activation improves glucose homeostasis and insulin sensitivity [339]. These effects are achieved by suppressing the expression of phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase) [339,340], and sterol regulatory element-binding protein 1c (SREBP1c) [341]. A very similar phenotype has been associated with PXR activation [288,289,342].…”