Hepatocyte-specific mutation establishes retinoid X receptor alpha as a heterodimeric integrator of multiple physiological processes in the liver

A large number of physiological processes in the adult liver are regulated by nuclear receptors that require heterodimerization with retinoid X recept ors (RXRs). In this study, we have used cre-mediated recombination to disru pt the mouse RXR alpha gene specifically in hepatocytes. Although such mice are viable, molecular and biochemical parameters indicate that every one o f the examined metabolic pathways in the liver (mediated by RXR heterodimer ization with PPAR alpha, CAR beta, PXR, LXR, and FXR) is compromised in the absence of RXR alpha. These data demonstrate the presence of a complex cir cuitry in which RXR alpha is integrated into a number of diverse physiologi cal pathways as a common regulatory component of cholesterol, fatty acid, b ile acid, steroid, and xenobiotic metabolism and homeostasis.