HDL biology
CETP transgene expression reverses the cholesterol-raising effect of LXR agonists and instead lowers hepatic cholesterol while boosting biliary excretion in mice (J Lipid Res 2004)
Original title: Cholesteryl ester transfer protein modulates the effect of liver X receptor agonists on cholesterol transport and excretion in the mouse
Since liver X receptor (LXR), an oxysterol-activated nuclear receptor, induces cholesteryl ester transfer protein (CETP) transcription via a direct repeat 4 element in the CETP gene promoter, wild-type and CETP-expressing humanized mice were treated for 5 days with the LXR agonist T0901317 to assess the in vivo consequences for plasma lipids and hepatic and biliary lipid content. Treatment markedly raised hepatic CETP mRNA and plasma CETP activity. The 2-fold rise in total and HDL cholesterol seen in treated wild-type mice was absent in CETP transgenic (CETPTg) mice, and LXR agonist treatment reversed the hepatic cholesterol accumulation seen in CETPTg mice. LXR activation induced a 2-fold increase in hepatic LDL-receptor expression in both wild-type and CETPTg mice, and produced a significantly greater rise in biliary cholesterol in CETPTg mice than wild-type mice.
Original abstract
Human plasma, unlike mouse plasma, contains the cholesteryl ester transfer protein (CETP) that may influence the reverse cholesterol transport. Liver X receptor (LXR), an oxysterol-activated nuclear receptor induces CETP transcription via a direct repeat 4 element in the CETP gene promoter. The aim of the study was to assess in vivo the impact of LXR activation on CETP expression and its consequences on plasma lipid metabolism and hepatic and bile lipid content. Wild-type and humanized mice expressing CETP were treated for five days with T0901317 LXR agonist. This treatment produced marked rises in both hepatic CETP mRNA and plasma CETP activity levels. Interestingly, the LXR agonist-mediated, 2-fold rise in both total and HDL cholesterol levels in treated wild-type mice was not observed in CETPTg mice, and the accumulation of cholesterol in the liver of CETPTg mice was reversed by LXR agonist treatment. Moreover, LXR activation induced a 2-fold increase in hepatic LDL-receptor expression in wild-type and CETPTg mice, and it produced a significantly greater rise in biliary cholesterol concentration in CETPTg mice as compared with wild-type mice. In conclusion, induction of CETP constitutes a major determinant of the effect of LXR agonists on cholesterol transport and excretion.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.