Agonists of liver X receptors (LXR) α and β are important regulators of cholesterol metabolism, but agonism of the LXRα subtype appears to cause hepatic lipogenesis, suggesting LXRβ-selective activators are attractive new lipid lowering drugs. In this work, pharmacophore modeling and shape-based virtual screening were combined to predict new LXRβ-selective ligands. Out of the 10 predicted compo...

OBJECTIVE Liver X receptor (LXR) activators decrease atherosclerosis in mice. LXR activators (1) directly upregulate genes involved in reverse cholesterol transport and (2) exert anti-inflammatory effects mediated by transrepression of nuclear factor-κB target genes. We investigated whether myeloid cell deficiency of ATP-binding cassette transporters A1 and G1 (ABCA1/G1), principal targets of L...

BACKGROUND Liver X receptor (LXR) is a nuclear receptor presenting in macrophages; it works indispensably in lipid metabolism control and also negatively regulates the expression of inflammatory genes in macrophages. There are many LXR-related studies in adults with metabolic syndrome but rare reports in obese children with obstructive sleep apnea-hypopnea syndrome (OSAHS). The aim of this stud...

Liver X receptors (LXRs) exert key functions in lipid homeostasis and in control of inflammation. In this study we have explored the impact of LXR activation on the macrophage response to the endogenous inflammatory cytokine IFN-γ. Transcriptional profiling studies demonstrate that ∼38% of the IFN-γ-induced transcriptional response is repressed by LXR activation in macrophages. LXRs also mediat...

A critical event in the development of atherosclerosis is the recruitment of macrophages to the underlying epithelial layer of blood vessel walls and the uncontrolled uptake of oxi-dized/modified cholesterol. Continued accumulation of oxi-dized/modified cholesterol by macrophages and an associated inflammatory response leads to foam cell formation and the initiation of atherosclerosis. 1 Revers...

Insulin is a central regulator of glycolysis and de novo lipogenesis in the liver. However, hepatic glucose metabolism has been shown to activate the transcription of glycolytic and lipogenic enzymes independently of insulin. The nuclear liver X receptors LXR and LXR play a major role in glucose and lipid metabolism, regulating transcription of glycolytic and lipogenic enzymes in liver, which...

Sterol regulatory element-binding protein-1c (SREBP-1c) enhances transcription of genes encoding enzymes of unsaturated fatty acid biosynthesis in liver. SREBP-1c mRNA is known to increase when cells are treated with agonists of liver X receptor (LXR), a nuclear hormone receptor, and to decrease when cells are treated with unsaturated fatty acids, the end products of SREBP-1c action. Here we sh...

BACKGROUND/AIM Liver X receptors (LXRs) are ligand-activated transcription factors that were shown to stimulate hepatic lipogenesis leading to liver steatosis and hypertriglyceridemia. Despite their pro-lipogenic action, LXR activators normalize glycemia and improve insulin sensitivity in rodent models of type 2 diabetes. Antidiabetic action of LXR agonists is thought to result from suppression...

Atherosclerosis is considered to be a combined disorder of lipid metabolism and chronic inflammation. Recent studies have reported that liver X receptors (LXRs) are involved in lipid metabolism and inflammation and that LXR agonists inhibit atherogenesis. In contrast, angiotensin II is well known to accelerate atherogenesis through activation of the angiotensin II type 1 receptor (AT1R). To bet...