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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, RESULTS. Meshes: ATP Binding Cassette Transporter 1, ATP-Binding Cassette Transporters, Animals, Apolipoprotein A-I, Atherosclerosis, Cholesterol, HDL, Cholic Acid, Down-Regulation, Gene Expression, Humans, Liver, Male, Mice, Mice, Mutant Strains, Pregnane X Receptor, RNA, Messenger, Receptors, Cytoplasmic and Nuclear, Receptors, Steroid.
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Does expression of the pregnane X receptor in mice antagonize the cholic acid-mediated changes in plasma lipoprotein profile? Context: Modification of lipoprotein metabolism by bile acids has been mainly explained by activation of the farnesyl X receptor (FXR). The aim of the present study was to determine the relative contribution of the pregnane X receptor (PXR), another bile acid-activated nuclear receptor to changes in plasma lipoprotein profile. Wild-type mice, Pxr-deficient mice, and Pxr-null mice expressing human PXR (Pxr-null SXR-Tg mice) were fed a cholic acid-containing diet, and consequences on plasma lipoprotein profiles and target gene expression were assessed. Cholic acid produced significant decreases in high-density lipoprotein (HDL) cholesterol, plasma apolipoprotein (apo)A-I and hepatic apoA-I mRNA in wild-type mice. Interestingly, the effect of cholic acid was significantly more pronounced in Pxr-deficient mice, indicating that PXR contributes to the weakening of the effect of bile acids on lipoprotein metabolism. Reciprocally, changes in HDL/apoA-I profiles were abolished in Pxr-null SXR-Tg mice in which PXR-responsive genes, particularly those involved in bile acid detoxification were readily activated after cholic acid treatment.
assistant
PXR expression in mice antagonizes the cholic acid-mediated downregulation of plasma HDL cholesterol and apoA-I, and magnification of PXR/SXR-mediated changes may constitute a new mean to counteract the effects of bile acids on plasma lipoproteins. Final Decision: yes