Mechanisms
CETP levels track with bile acid concentration in children with Alagille syndrome cholestasis (Atherosclerosis 2008)
Original title: Fluctuation of lipoprotein metabolism linked with bile acid-activated liver nuclear receptors in Alagille syndrome
Researchers studied three children with Alagille syndrome (AGS), a rare hereditary disorder causing fluctuating cholestasis and dyslipidemia, and their three incompletely affected parents, tracking blood bile acid and lipoprotein levels alongside hepatic nuclear receptor expression over several years. In the AGS children, total bile acid (TBA) level correlated positively with LDL cholesterol, apoE-rich HDL cholesterol, apoA-I, apoE, and CETP concentrations, but negatively with apoE-poor HDL cholesterol. Liver biopsy Western blotting showed farnesoid X receptor and liver X receptor expression rose in parallel with TBA level, as did CETP and ABCA1 expression, while scavenger receptor class B type-I expression moved in the opposite direction and apoA-I expression stayed near control levels regardless of TBA. In the incompletely affected parents, bile acid and lipoprotein parameters showed little fluctuation. The authors conclude cholestasis is closely linked to dyslipidemia and hepatic nuclear receptor expression, including CETP, in Alagille syndrome.
Original abstract
Alagille syndrome (AGS) is a rare hereditary disorder exhibiting fluctuating cholestasis and dyslipidemia. Farnesoid X receptor (FXR) and liver X receptor (LXR) are hepatic nuclear receptors that regulate bile acid and lipoprotein metabolism. To investigate whether cholestasis is related to dyslipidemia and hepatic nuclear receptor expression in AGS patients, we determined the blood levels of total bile acid (TBA) and lipoprotein parameters, and examined hepatic nuclear receptor expression in three AGS children and their three incomplete AGS parents repeatedly over several years. In the AGS children, TBA level showed significant positive correlations with low-density lipoprotein-cholesterol, apolipoprotein E (apoE)-rich high-density lipoprotein-cholesterol (HDL-C), apoA-I, apoE, and cholesteryl ester transfer protein (CETP) concentrations, but negative correlation with apoE-poor HDL-C concentration. Western blot analysis of liver biopsy specimens revealed that FXR and LXR expression increased in parallel with TBA level. CETP- and ATP-binding cassette transporter A1 expression also increased with TBA level, while scavenger receptor class B type-I expression showed the opposite response. However, apoA-I expression was similar to the control level at any TBA level. In the incomplete AGS parents, TBA and lipoprotein parameters showed little fluctuation. In summary, cholestasis is closely related to dyslipidemia and hepatic nuclear receptor expression in AGS patients.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.