ABCA1-dependent lipid efflux to apolipoprotein A-I mediates HDL particle formation and decreases VLDL secretion from murine hepatocytes. J Lipid Res 2004 Jun;45(6):1122-31
Date
03/03/2004Pubmed ID
14993246DOI
10.1194/jlr.M300529-JLR200Scopus ID
2-s2.0-2542484330 (requires institutional sign-in at Scopus site) 75 CitationsAbstract
High levels of expression of the ATP binding cassette transporter A1 (ABCA1) in the liver and the need to over- or underexpress hepatic ABCA1 to impact plasma HDL levels in mice suggest a major role of the liver in HDL formation and in determining circulating HDL levels. Cultured murine hepatocytes were used to examine the role of hepatic ABCA1 in mediating the lipidation of apolipoprotein A-I (apoA-I) for HDL particle formation. Exogenous apoA-I stimulated cholesterol efflux to the medium from wild-type hepatocytes, but not from ABCA1-deficient (abca1(-/-)) hepatocytes. ApoA-I induced the formation of new HDL particles and enhanced the lipidation of endogenously secreted murine apoA-I in ABCA1-expressing but not abca1(-/-) hepatocytes. ABCA1-dependent cholesterol mobilization to apoA-I increased new cholesterol synthesis, indicating depletion of the regulatory pool of hepatocyte cholesterol during HDL formation. Secretion of triacylglycerol and apoB was decreased following apoA-I incubation with ABCA1-expressing but not abca1(-/-) hepatocytes. These results support a major role for hepatocyte ABCA1 in generating a critical pool of HDL precursor particles that enhance further HDL generation and passive cholesterol mobilization in the periphery. The results also suggest that diversion of hepatocyte cholesterol into the "reverse" cholesterol transport pathway diminishes cholesterol availability for apoB-containing lipoprotein secretion by the liver.
Author List
Sahoo D, Trischuk TC, Chan T, Drover VA, Ho S, Chimini G, Agellon LB, Agnihotri R, Francis GA, Lehner RAuthor
Daisy Sahoo PhD Dean, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ATP Binding Cassette Transporter 1ATP-Binding Cassette Transporters
Animals
Apolipoprotein A-I
Apolipoproteins B
Cells, Cultured
Cholesterol
Female
Hepatocytes
Lipoproteins, HDL
Lipoproteins, VLDL
Male
Mice
Mice, Knockout
Rats
Rats, Sprague-Dawley
