ABCG1 has a critical role in mediating cholesterol efflux to HDL and preventing cellular lipid accumulation

Cell Metab. 2005 Feb;1(2):121-31. doi: 10.1016/j.cmet.2005.01.002.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 1
  • ATP-Binding Cassette Transporters / physiology*
  • Animals
  • Azo Compounds / pharmacology
  • Cholesterol / metabolism*
  • Coloring Agents / pharmacology
  • Female
  • Gene Expression Regulation*
  • Hepatocytes / cytology
  • Hepatocytes / metabolism
  • Humans
  • In Situ Hybridization
  • Lac Operon
  • Lipid Metabolism*
  • Lipoproteins / physiology*
  • Lipoproteins, HDL / metabolism*
  • Liver / metabolism
  • Lung / metabolism
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • RNA / metabolism
  • RNA, Messenger / metabolism

Substances

  • ABCG1 protein, mouse
  • ATP Binding Cassette Transporter, Subfamily G, Member 1
  • ATP-Binding Cassette Transporters
  • Azo Compounds
  • Coloring Agents
  • Lipoproteins
  • Lipoproteins, HDL
  • RNA, Messenger
  • RNA
  • Cholesterol
  • oil red O