Hematopoietic ABCA1 deletion promotes monocytosis and worsens diet-induced insulin resistance in mice

J Lipid Res. 2016 Jan;57(1):100-8. doi: 10.1194/jlr.M064303. Epub 2015 Nov 3.


Low-grade chronic inflammation plays an important role in the pathogenesis of obesity-induced insulin resistance. ABCA1 is essential for reverse cholesterol transport and HDL synthesis, and protects against macrophage inflammation. In the present study, the effects of ABCA1 deficiency in hematopoietic cells on diet-induced inflammation and insulin resistance were tested in vivo using bone marrow transplanted (BMT)-WT and BMT-ABCA1(-/-) mice. When challenged with a high-fat high-carbohydrate diabetogenic diet with added cholesterol (HFHSC), BMT-ABCA1(-/-) mice displayed enhanced insulin resistance and impaired glucose tolerance as compared with BMT-WT mice. The worsened insulin resistance and impaired glucose tolerance in BMT-ABCA1(-/-) mice were accompanied by increased macrophage accumulation and inflammation in adipose tissue and liver. Moreover, BMT-ABCA1(-/-) mice had significantly higher hematopoietic stem cell proliferation, myeloid cell expansion, and monocytosis when challenged with the HFHSC diet. In vitro studies indicated that macrophages from ABCA1(-/-) mice showed significantly increased inflammatory responses induced by saturated fatty acids. Taken together, these studies point to an important role for hematopoietic ABCA1 in modulating a feed-forward mechanism in obesity such that inflamed tissue macrophages stimulate the production of more monocytes, leading to an exacerbation of inflammation and associated disease processes.

Keywords: ATP binding cassette transporter A1; adipose tissue; cholesterol; diabetes; high density lipoprotein; macrophages; obesity.

Publication types

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

MeSH terms

  • ATP Binding Cassette Transporter 1 / blood
  • ATP Binding Cassette Transporter 1 / deficiency*
  • ATP Binding Cassette Transporter 1 / genetics
  • Adipose Tissue / metabolism
  • Animals
  • Cholesterol / metabolism
  • Cholesterol / pharmacology
  • Diet, High-Fat
  • Glucose Intolerance / metabolism
  • Inflammation / metabolism
  • Inflammation / pathology
  • Insulin Resistance / physiology*
  • Liver / metabolism
  • Macrophages / metabolism
  • Macrophages / pathology
  • Male
  • Mice
  • Mice, Inbred DBA
  • Monocytes / metabolism
  • Monocytes / pathology
  • Myeloproliferative Disorders / genetics
  • Myeloproliferative Disorders / metabolism
  • Myeloproliferative Disorders / pathology
  • Obesity / pathology
  • Receptors, LDL / metabolism


  • ABCA1 protein, mouse
  • ATP Binding Cassette Transporter 1
  • Receptors, LDL
  • Cholesterol