Nascent HDL formation in hepatocytes and role of ABCA1, ABCG1, and SR-BI

Ailing Ji, Joanne M. Wroblewski, Lei Cai, Maria C. De Beer, Nancy R. Webb, Deneys R. Van Der Westhuyzen

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

To study the mechanisms of hepatic HDL formation, we investigated the roles of ABCA1, ABCG1, and SR-BI in nascent HDL formation in primary hepatocytes isolated from mice deficient in ABCA1, ABCG1, or SR-BI and from wild-type (WT) mice. Under basal conditions, in WT hepatocytes, cholesterol efflux to exogenous apoA-I was accompanied by conversion of apoA-I to HDL-sized particles. LXR activation by T0901317 markedly enhanced the formation of larger HDL-sized particles as well as cellular cholesterol efflux to apoA-I. Glyburide treatment completely abolished the formation of 7.4 nm diameter and greater particles but led to the formation of novel 7.2 nm-sized particles. However, cells lacking ABCA1 failed to form such particles. ABCG1-deficient cells showed similar capacity to efflux cholesterol to apoA-I and to form nascent HDL particles compared with WT cells. Cholesterol efflux to apoA-I and nascent HDL formation were slightly but significantly enhanced in SR-BI-deficient cells compared with WT cells under basal but not LXR activated conditions. As in WT but not in ABCA1-deficient hepatocytes, 7.2 nm-sized particles generated by glyburide treatment were also detected in ABCG1-deficient and SR-BI-deficient hepatocytes. Our data indicate that hepatic nascent HDL formation is highly dependent on ABCA1 but not on ABCG1 or SR-BI.

Original languageEnglish
Pages (from-to)446-455
Number of pages10
JournalJournal of Lipid Research
Volume53
Issue number3
DOIs
StatePublished - Mar 2012

Keywords

  • ATP binding cassette transporter A1
  • ATP binding cassette transporter G1
  • Cholesterol efflux
  • Class B scavenger receptor type 1
  • Hepatocyte
  • High density lipoprotein formation

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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