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Updated: May 6, 2026
Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
Published on: April 3, 2017
Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis
Liza Makowski1, Jeffrey B Boord2, Kazuhisa Maeda1
1Division of Biological Sciences and Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.
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.
Insights
Adipocyte fatty-acid-binding protein (aP2) in macrophages contributes to atherosclerosis. Reducing aP2 in macrophages protects against atherosclerosis, independent of its role in adipocytes, offering a potential therapeutic target.
Area of Science:
- Biochemistry
- Immunology
- Metabolic Syndrome
Background:
- Adipocyte fatty-acid-binding protein (aP2) is crucial for insulin resistance and lipid metabolism.
- The role of aP2 in macrophages and its contribution to atherosclerosis were previously unclear.
Purpose of the Study:
- To investigate the role of aP2 in macrophage biology.
- To determine the contribution of macrophage aP2 to the development of atherosclerosis.
Main Methods:
- Apolipoprotein E (ApoE)-deficient mice lacking aP2 were studied.
- Bone-marrow transplantation was used to create mice with specific aP2 deficiencies in adipocytes and macrophages.
- Macrophage responses to modified lipoproteins were assessed.
Main Results:
- Mice deficient in both ApoE and aP2 were protected from atherosclerosis without changes in serum lipids or insulin sensitivity.
- aP2-deficient macrophages exhibited altered inflammatory cytokine production and reduced cholesterol ester accumulation.
- Bone-marrow chimeric mice demonstrated that macrophage aP2 independently contributes to atherogenesis.
Conclusions:
- Macrophage aP2 plays a significant role in the development of atherosclerosis.
- aP2 links metabolic syndrome features to atherosclerosis, suggesting it as a therapeutic target for preventing cardiovascular disease.
