We explored the effects of bile acids on triglyceride (TG) homeostasis using a combination of molecular, cellular, and animal models. Cholic acid (CA) prevents hepatic TG accumulation, VLDL secretion, and elevated serum TG in mouse models of hypertriglyceridemia. At the molecular level, CA decreases hepatic expression of SREBP-1c and its lipogenic target genes. Through the use of mouse mutants ...

The nuclear receptors liver X receptor (LXR)alpha and LXRbeta are sensors of cholesterol metabolism and lipid biosynthesis. They have recently been found to be regulators of inflammatory cytokines, suppressors of hepatic glucose production, and involved in different cell-signaling pathways. LXRalpha is a target gene of the peroxisome proliferator-activated receptor-gamma, a target of drugs used...

The liver X receptors alpha and beta (LXRalpha and LXRbeta) are members of the nuclear receptor family of proteins that are critical for the control of lipid homeostasis in vertebrates. The endogenous activators of these receptors are oxysterols and intermediates in the cholesterol biosynthetic pathway. LXRs serve as cholesterol sensors that regulate the expression of multiple genes involved in...

Liver X receptor (LXR) is an attractive drug target for the development of novel therapeutic agents for the treatment of dyslipidaemia and cholestasis. In the present work, comparative molecular field analysis (CoMFA) and hologram quantitative structure-activity relationship (HQSAR) studies were conducted on a series of potent LXR ligands. Significant correlation coefficients (CoMFA, r(2) = 0.9...

Previous work has implicated PPAR gamma in the regulation of CD36 expression and macrophage uptake of oxidized LDL (oxLDL). We provide evidence here that in addition to lipid uptake, PPAR gamma regulates a pathway of cholesterol efflux. PPAR gamma induces ABCA1 expression and cholesterol removal from macrophages through a transcriptional cascade mediated by the nuclear receptor LXR alpha. Ligan...

Apolipoprotein M (apoM) has been suggested to play a role in reverse cholesterol transport. Here we studied the influence of liver X-receptor (LXR) agonist on the transcriptional regulation of apoM. Studies were performed in murine liver and intestinal mucosal cells in vivo and in human intestinal Caco-2 cells in vitro. The expression of apoM was analyzed by quantitative real time PCR, and comp...

Metabolic pulse-chase experiments demonstrated that 25-hydroxycholesterol (25-OH), the endogenous activator of the liver X receptor (LXR), significantly reduced the biosynthesis of phosphatidylethanolamine via CDP-ethanolamine (Kennedy) pathway at the step catalyzed by CTP: phosphoethanolamine cytidylyltransferase (Pcyt2). In the mouse embryonic fibroblasts C3H10T1/2, the LXR synthetic agonist ...

Several of the ATP binding cassette (ABC) transporters have recently been shown to play important roles in reverse cholesterol transport (RCT) and prevention of atherosclerosis. In the liver, ABCG5 and ABCG8 have been proposed to efflux sterols into the bile for excretion. ABCG5 and ABCG8 also limit absorption of dietary cholesterol and plant sterols in the intestine. In macrophages, ABCA1 and ...

The liver X receptors (LXRs) are nuclear receptors with established roles in the regulation of lipid metabolism. We now show that LXR signaling not only regulates macrophage cholesterol metabolism but also impacts antimicrobial responses. Mice lacking LXRs are highly susceptible to infection with the intracellular bacteria Listeria monocytogenes (LM). Bone marrow transplant studies point to alt...

BACKGROUND Liver X receptors (LXRs) are ligand-activated transcription factors involved in the control of lipid metabolism and inflammation. Synthetic LXR agonists have been shown to inhibit the progression of atherosclerosis in mice, but the mechanism is uncertain. LXR agonism upregulates the genes encoding ATP binding cassette transporters A1 (ABCA1) and G1 (ABCG1) in macrophages, thus promot...