ABCG1 has a critical role in mediating cholesterol efflux to HDL and preventing cellular lipid accumulation.
Here we demonstrate that the ABC transporter ABCG1 plays a critical role in lipid homeostasis by controlling both tissue lipid levels and the efflux of cellular cholesterol to HDL. Targeted disruption of Abcg1 in mice has no effect on plasma lipids but results in massive accumulation of both neutral lipids and phospholipids in hepatocytes and in macrophages within multiple tissues following administration of a high-fat and -cholesterol diet. In contrast, overexpression of human ABCG1 protects murine tissues from dietary fat-induced lipid accumulation. Finally, we show that cholesterol efflux to HDL specifically requires ABCG1, whereas efflux to apoA1 requires ABCA1. These studies identify Abcg1 as a key gene involved in both cholesterol efflux to HDL and in tissue lipid homeostasis.
Kennedy
Matthew A
MA
Department of Biological Chemistry, CHS 33-257, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, California 90095, USA.
Barrera
Gabriel C
GC
Nakamura
Kotoka
K
Baldán
Angel
A
Tarr
Paul
P
Fishbein
Michael C
MC
Frank
Joy
J
Francone
Omar L
OL
Edwards
Peter A
PA
D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology; D002784:Cholesterol / Q000378:metabolism*; D004396:Coloring Agents / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D007763:Lac Operon; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000502:physiology*; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
C487540:ABCG1 protein, mouse; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D001391:Azo Compounds; D004396:Coloring Agents; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D012333:RNA, Messenger; D012313:RNA; D002784:Cholesterol; C011049:oil red O