Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis

Liza Makowski, Jeffrey B. Boord, Kazuhisa Maeda, Vladimir R. Babaev, K. Teoman Uysal, Maureen A. Morgan, Rex A. Parker, Jill Suttles, Sergio Fazio, Gökhan S. Hotamisligil, MacRae F. Linton

Research output: Contribution to journalArticle

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Abstract

The adipocyte fatty-acid-binding protein, aP2, has an important role in regulating systemic insulin resistance and lipid metabolism. Here we demonstrate that aP2 is also expressed in macrophages, has a significant role in their biological responses and contributes to the development of atherosclerosis. Apolipoprotein E (ApoE)-deficient mice also deficient for aP2 showed protection from atherosclerosis in the absence of significant differences in serum lipids or insulin sensitivity. aP2-deficient macrophages showed alterations in inflammatory cytokine production and a reduced ability to accumulate cholesterol esters when exposed to modified lipoproteins. Apoe-/- mice with Ap2+/+ adipocytes and Ap2-/- macrophages generated by bone-marrow transplantation showed a comparable reduction in atherosclerotic lesions to those with total aP2 deficiency, indicating an independent role for macrophage aP2 in atherogenesis. Through its distinct actions in adipocytes and macrophages, aP2 provides a link between features of the metabolic syndrome and could be a new therapeutic target for the prevention of atherosclerosis.

Original languageEnglish (US)
Pages (from-to)699-705
Number of pages7
JournalNature Medicine
Volume7
Issue number6
DOIs
StatePublished - 2001
Externally publishedYes

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Fatty Acid-Binding Proteins
Macrophages
Apolipoproteins E
Atherosclerosis
Adipocytes
Insulin Resistance
Insulin
Cholesterol Esters
Bone Marrow Transplantation
Lipid Metabolism
Lipoproteins
Bone
Cytokines
Lipids
Serum

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Makowski, L., Boord, J. B., Maeda, K., Babaev, V. R., Uysal, K. T., Morgan, M. A., ... Linton, M. F. (2001). Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis. Nature Medicine, 7(6), 699-705. https://doi.org/10.1038/89076

Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis. / Makowski, Liza; Boord, Jeffrey B.; Maeda, Kazuhisa; Babaev, Vladimir R.; Uysal, K. Teoman; Morgan, Maureen A.; Parker, Rex A.; Suttles, Jill; Fazio, Sergio; Hotamisligil, Gökhan S.; Linton, MacRae F.

In: Nature Medicine, Vol. 7, No. 6, 2001, p. 699-705.

Research output: Contribution to journalArticle

Makowski, L, Boord, JB, Maeda, K, Babaev, VR, Uysal, KT, Morgan, MA, Parker, RA, Suttles, J, Fazio, S, Hotamisligil, GS & Linton, MF 2001, 'Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis', Nature Medicine, vol. 7, no. 6, pp. 699-705. https://doi.org/10.1038/89076
Makowski, Liza ; Boord, Jeffrey B. ; Maeda, Kazuhisa ; Babaev, Vladimir R. ; Uysal, K. Teoman ; Morgan, Maureen A. ; Parker, Rex A. ; Suttles, Jill ; Fazio, Sergio ; Hotamisligil, Gökhan S. ; Linton, MacRae F. / Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis. In: Nature Medicine. 2001 ; Vol. 7, No. 6. pp. 699-705.
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