Intestinal ABCA1 directly contributes to HDL biogenesis in vivo.

TitleIntestinal ABCA1 directly contributes to HDL biogenesis in vivo.
Publication TypeJournal Article
Year of Publication2006
AuthorsBrunham, LR, Kruit, JK, Iqbal, J, Fievet, C, Timmins, JM, Pape, TD, Coburn, BA, Bissada, N, Staels, B, Groen, AK, M Hussain, M, Parks, JS, Kuipers, F, Hayden, MR
JournalJ Clin Invest
Volume116
Issue4
Pagination1052-62
Date Published2006 Apr
ISSN0021-9738
KeywordsAnimals, ATP Binding Cassette Transporter 1, ATP-Binding Cassette Transporters, Cholesterol, HDL, Fluorescent Antibody Technique, Intestines, Lymph, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic
Abstract

Plasma HDL cholesterol levels are inversely related to risk for atherosclerosis. The ATP-binding cassette, subfamily A, member 1 (ABCA1) mediates the rate-controlling step in HDL particle formation, the assembly of free cholesterol and phospholipids with apoA-I. ABCA1 is expressed in many tissues; however, the physiological functions of ABCA1 in specific tissues and organs are still elusive. The liver is known to be the major source of plasma HDL, but it is likely that there are other important sites of HDL biogenesis. To assess the contribution of intestinal ABCA1 to plasma HDL levels in vivo, we generated mice that specifically lack ABCA1 in the intestine. Our results indicate that approximately 30% of the steady-state plasma HDL pool is contributed by intestinal ABCA1 in mice. In addition, our data suggest that HDL derived from intestinal ABCA1 is secreted directly into the circulation and that HDL in lymph is predominantly derived from the plasma compartment. These data establish a critical role for intestinal ABCA1 in plasma HDL biogenesis in vivo.

DOI10.1172/JCI27352
Alternate JournalJ. Clin. Invest.
PubMed ID16543947
PubMed Central IDPMC1401485
Grant ListDK46900 / DK / NIDDK NIH HHS / United States
HL07115 / HL / NHLBI NIH HHS / United States
HL49373 / HL / NHLBI NIH HHS / United States
HL64272 / HL / NHLBI NIH HHS / United States