Angiopoietin-Like 3 (ANGPTL3) is a direct target gene of the LXR:RXR heterodimer. Synthetic and endogenous oxysterol ligand administration to human HepG2 cells or mice results in increased mRNA and protein levels of ANGPTL3 (Kaplan R et al. 2003). An LXR response element (LXRE) was identified in the promoter of human ANGPTL3 which conferred ligand and receptor-specific regulation in luciferase cell reporter assays (Kaplan R et al. 2003). ANGPTL3 is a secreted protein that inhibits activity of lipoprotein lipase and endothelial lipase (Shimizugawa T et al. 2002), and the LXR-mediated upregulation of this gene likely contributes (along with hepatic lipogenesis) to the severe hypertriglyceridemia associated with use of LXR drugs (Inaba T et al. 2003)
Hernandez, M, Wright, SD, Waters, MG, Gan, FX, Kaplan, R, Zhang, T, Cai, TQ
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