Combined adipocyte-macrophage fatty acid-binding protein deficiency improves metabolism, atherosclerosis, and survival in apolipoprotein E-deficient mice

Jeffrey B. Boord, Kazuhisa Maeda, Liza Makowski, Vladimir R. Babaev, Sergio Fazio, MacRae F. Linton, Gökhan S. Hotamisligil

Research output: Contribution to journalArticlepeer-review

150 Scopus citations

Abstract

Background-The adipocyte fatty acid-binding protein (FABP) aP2 is expressed by adipocytes and macrophages and modulates insulin resistance, glucose and lipid metabolism, and atherosclerosis. Insulin sensitivity is improved in obese but not in lean aP2-deficient mice. A second fatty acid-binding protein, mall, also is expressed in adipocytes and macrophages, and mall deficiency produces similar effects on insulin resistance. We tested the hypothesis that combined aP2 and mall deficiency would produce synergistic effects on metabolism and reduce atherosclerosis in apolipoprotein E-deficient (apoE-/-) mice. Methods and Results-Male and female apoE-/- mice null for both aP2 and mall (3KO) and apoE-/- controls were fed a low-fat chow diet for 16 or 56 weeks. Lean 3KO mice had significantly lower serum cholesterol and triglycerides as well as improved insulin and glucose tolerance as compared with controls. Analysis of atherosclerotic lesions in the 3KO mice showed dramatic reductions in both early (20 weeks) and late-stage (60 weeks) atherosclerosis. Strikingly, survival in the 3KO mice was improved by 67% as compared with apoE-/- controls when challenged with the Western diet for 1 year. Conclusions-Combined aP2 and mall deficiency improved glucose and lipid metabolism, reduced atherosclerosis, and improved survival in apoE-/- mice, making these proteins important therapeutic targets for the prevention of the cardiovascular consequences of the metabolic syndrome.

Original languageEnglish (US)
Pages (from-to)1492-1498
Number of pages7
JournalCirculation
Volume110
Issue number11
DOIs
StatePublished - Sep 14 2004
Externally publishedYes

Keywords

  • Atherosclerosis
  • Macrophages
  • Metabolism
  • Syndrome X

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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