出版社：American Society for Biochemistry and Molecular Biology
摘要：The impact of apolipoprotein C-I (apoC-I) deficiency on hepaticlipid metabolism was addressed in mice in the presence or theabsence of cholesteryl ester transfer protein (CETP). In additionto the expected moderate reduction in plasma cholesterol levels,apoCIKO mice showed significant increases in the hepatic contentof cholesteryl esters (+58%) and triglycerides (+118%) and inbiliary cholesterol concentration (+35%) as compared with wild-typemice. In the presence of CETP, hepatic alterations resultingfrom apoC-I deficiency were enforced, with up to 58% and 302%increases in hepatic levels of cholesteryl esters and triglyceridesin CETPTg/apoCIKO mice versus CETPTg mice, respectively. Biliarylevels of cholesterol, phospholipids, and bile acids were increasedby 88, 77, and 20%, respectively, whereas total cholesterol,HDL cholesterol, and triglyceride concentrations in plasma werefurther reduced in CETPTg/apoCIKO mice versus CETPTg mice. Finally,apoC-I deficiency was not associated with altered VLDL productionrate. In line with the previously recognized inhibition of lipoproteinclearance by apoC-I, apoC-I deficiency led to decreased plasmalipid concentration, hepatic lipid accumulation, and increasedbiliary excretion of cholesterol. The effect was even greaterwhen the alternate reverse cholesterol transport pathway viaVLDL/LDL was boosted in the presence of CETP.Supplementary key words liver • bile • cholesterol • triglycerides
Abbreviations: ABCB4, ATP binding cassette B4; ALAT, alanine transaminase; apoC-I, apolipoprotein C-I; ASAT, aspartate transaminase; CETP, cholesteryl ester transfer protein; LPL, lipoprotein lipase; NBD-CE, nitrobenzoxadiazole-labeled cholesteryl esters
