Impaired cholesterol metabolism and enhanced atherosclerosis in clock mutant mice.

ABSTRACT:

Background

Clock is a key transcription factor that positively controls circadian regulation. However, its role in plasma cholesterol homeostasis and atherosclerosis has not been studied.

Methods and results

We show for the first time that dominant-negative Clock mutant protein (Clock(Δ19/Δ19)) enhances plasma cholesterol and atherosclerosis in 3 different mouse models. Detailed analyses revealed that Clk(Δ19/Δ19)Apoe(-/-) mice display hypercholesterolemia resulting from the accumulation of apolipoprotein B48-containing cholesteryl ester-rich lipoproteins. Physiological studies showed that enhanced cholesterol absorption by the intestine contributes to hypercholesterolemia. Molecular studies indicated that the expression of Niemann Pick C1 Like 1, Acyl-CoA:Cholesterol acyltr

SUBMITTER: Pan X 

PROVIDER: S-EPMC3897228 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature