Differential expression of cholesteryl ester transfer protein in the liver and plasma of fasted and fed transgenic mice

Abstract

Because cholesteryl ester transfer protein (CETP) is considered a potential target in the treatment of atherosclerosis, several reports have focused on the regulation of this enzyme, and there is evidence that insulin may be a regulatory factor. The present study examines the differential expression of the human CETP gene between physiologic conditions that are accompanied by low (fasted) and high (fed) insulin levels. CETP expression was examined in plasma and tissues of transgenic mice expressing the human CETP minigene after 12 hours of fasting ( n = 20) or ad libitum feeding ( n = 20) with normal mouse chow. Plasma cholesteryl ester transfer activity (CETA) was 20% higher in fed than in fasted mice, reflecting higher levels of CETP ( P < 0.05). This observation was accompanied by higher liver mRNA in fed mice (100%, P < 0.05), as determined by ribonuclease protection assays, as well as by higher CETA (23%, P < 0.05) and CETP mass (29%, P < 0.05) in the particulate fraction of liver homogenates. These parameters of liver CETP expression correlated well with each other, as well as with plasma CETA. CETP in the liver particulate fraction was found as a doublet (approximately 70 and 65 kDa), which resolved to a single band (approximately 60 kDa) upon deglycosylation. No differences in CETP expression were observed in pooled adipose tissue samples from fed and fasted mice. Insulin and glucose were not related to any plasma or tissue parameter of CETP expression. In summary, the concerted, differential expression of CETP in the liver of fed and fasted transgenic mice appears to contribute to higher plasma CETP levels in fed mice, but the precise role of insulin and glucose in regulating CETP expression under fasted and fed conditions needs to be defined.