Functions of cholesterol metabolites

Abstract

Cholesterol is a major component of membrane lipids. Thus, adjusting the membrane cholesterol composition is essential for maintaining cellular homeostasis. Cholesterol biosynthesis and uptake by LDL receptors are tightly regulated at the transcriptional level through negative feedback control, which is mediated by sterol regulatory element-binding proteins (SREBPs). In particular, SREBP-2 is activated in a cholesterol-dependent manner and, thus, is significantly involved in regulating the expression of those genes associated with cholesterol metabolism. Cholesterol metabolites such as oxysterols are involved in regulating sterol metabolism by binding to the nuclear receptor, liver X receptor (LXR). Cholesterol catabolites, i.e., bile acids, are agonists for another nuclear receptor, farnesoid X receptor (FXR), and a bile acid receptor, TGR5. Activated FXR regulates bile acid metabolism and TGR5 improves glucose metabolism through the actions of glucagon-like peptide-1 (GLP-1).