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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adipocytes / physiology*
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Animals
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Aorta / cytology
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Apolipoproteins E / metabolism*
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Arteriosclerosis / etiology
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Arteriosclerosis / physiopathology*
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Arteriosclerosis / prevention & control
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Bone Marrow Transplantation
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Carrier Proteins / metabolism*
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Cell Line
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Cholesterol Esters / metabolism
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Diet
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Fatty Acid-Binding Protein 7
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Fatty Acid-Binding Proteins
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Female
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Foam Cells / physiology
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Glucose / metabolism
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Humans
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Insulin / metabolism
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Interleukin-1 / genetics
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Interleukin-1 / metabolism
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Interleukin-6 / genetics
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Interleukin-6 / metabolism
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Lipids / blood
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Macrophages / physiology*
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Neoplasm Proteins*
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Nerve Tissue Proteins*
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
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Tumor Suppressor Proteins*
Substances
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Apolipoproteins E
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Carrier Proteins
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Cholesterol Esters
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FABP7 protein, human
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Fabp5 protein, mouse
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Fabp7 protein, mouse
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Fatty Acid-Binding Protein 7
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Fatty Acid-Binding Proteins
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Insulin
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Interleukin-1
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Interleukin-6
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Lipids
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Neoplasm Proteins
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Nerve Tissue Proteins
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Tumor Necrosis Factor-alpha
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Tumor Suppressor Proteins
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Glucose