Hepatic lipid accumulation in apolipoprotein CI-deficient mice is potentiated by cholesteryl ester transfer protein

Thomas Gautier, Uwe J.F. Tietge, Renze Boverhof, Frank G. Perton, Naig Le Guern, David Masson, Patrick C.N. Rensen, Louis M. Havekes, Laurent Lagrost, and Folkert Kuipers

Departement of Pediatrics - Center for Liver, Digestive and Metabolic Diseases, University Medical Center Groningen, Groningen 9713 GZ

Corresponding Author: t.gautier{at}med.umcg.nl

The impact of apolipoprotein (apo) CI deficiency on hepatic lipid metabolism was addressed in mice in the presence or in the absence of CETP. Besides the expected moderate reduction in plasma cholesterol levels, apoCIKO mice showed significant increases in the hepatic content of cholesteryl esters (+58%) and triglycerides (+118%) and in biliary cholesterol concentration (+35%) as compared to wild-type mice. In the presence of CETP, hepatic alterations resulting from apoCI deficiency were enforced, with up to 58% and 302% increases in hepatic levels of cholesteryl esters and triglycerides in CETPTg/apoCIKO mice versus CETPTg mice, respectively. Biliary levels of cholesterol, phospholipids and bile acids were increased by 88%, 77% and 20%, respectively, while total cholesterol, HDL cholesterol and triglyceride concentrations in plasma were further reduced in CETPTg/apoCIKO mice versus CETPTg mice. Finally, apoCI deficiency was not associated with altered VLDL production rate. In line with the previously recognized inhibition of lipoprotein clearance by apoCI, apoCI deficiency led to decreased plasma lipid concentration, hepatic lipid accumulation and increased biliary excretion of cholesterol. The effect was even greater when the alternate reverse cholesterol transport pathway via VLDL/LDL was boosted in the presence of CETP.

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

W. de Haan, J. de Vries-van der Weij, J. W.A. van der Hoorn, T. Gautier, C. C. van der Hoogt, M. Westerterp, J. A. Romijn, J. W. Jukema, L. M. Havekes, H. M.G. Princen, et al.
Torcetrapib Does Not Reduce Atherosclerosis Beyond Atorvastatin and Induces More Proinflammatory Lesions Than Atorvastatin
Circulation, May 13, 2008; 117(19): 2515 - 2522.
[Abstract] [Full Text] [PDF]

J. F. P. Berbee, S. P. Mooijaart, A. J. M. de Craen, L. M. Havekes, D. van Heemst, P. C. N. Rensen, and R. G. J. Westendorp
Plasma Apolipoprotein CI Protects Against Mortality From Infection in Old Age
J. Gerontol. A Biol. Sci. Med. Sci., February 1, 2008; 63(2): 122 - 126.
[Abstract] [Full Text] [PDF]

All ASBMB Journals	Journal of Biological Chemistry
Molecular and Cellular Proteomics	ASBMB Today

				J. F. P. Berbee, S. P. Mooijaart, A. J. M. de Craen, L. M. Havekes, D. van Heemst, P. C. N. Rensen, and R. G. J. Westendorp Plasma Apolipoprotein CI Protects Against Mortality From Infection in Old Age J. Gerontol. A Biol. Sci. Med. Sci., February 1, 2008; 63(2): 122 - 126. [Abstract] [Full Text] [PDF]