on August 8, 2002
Published online before print August 8, 2002, doi: 10.1161/01.ATV.0000033090.81345.E6
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Submitted on May 7, 2002
Accepted on July 26, 2002
Adipocyte Fatty Acid
Binding Protein, aP2, Alters Late Atherosclerotic Lesion Formation in Severe Hypercholesterolemia
Jeffrey B. Boord ;
From the Departments of Medicine (J.B.B., V.R.B., S.F., M.F.L.), Pathology (S.F.), and Pharmacology (M.F.L.), Vanderbilt University Medical Center, Nashville, Tenn, and the Division of Biological Sciences and Department of Nutrition (K.M., L.M., G.S.H.), Harvard School of Public Health, Boston, Mass.
* To whom correspondence should be addressed. E-mail: ghotamis{at}hsph.harvard.edu.
Objective—The adipocyte fatty acidbinding protein, aP2, has important effects on insulin resistance, lipid metabolism, and atherosclerosis. Its expression in macrophages enhances early foam cell formation and atherosclerosis in vivo. This study was designed to determine whether aP2 deficiency has a similar effect in the setting of advanced atherosclerosis and severe hypercholesterolemia.
Methods and Results—Mice deficient in aP2 and apolipoprotein E (aP2-/-apoE-/- mice) and apolipoprotein Edeficient control mice (apoE-/- mice) were fed a Western diet for 14 weeks. No significant differences in fasting serum levels of cholesterol, triglycerides, or free fatty acids were found between groups for each sex. Compared with apoE-/- control mice, male and female aP2-/-apoE-/- mice had significant reductions in mean atherosclerotic lesion size in the proximal aorta, en face aorta, and innominate/right carotid artery. Feeding the Western diet in the apoE-deficient background did not cause a significant reduction in insulin sensitivity in vivo, as determined by steady-state serum glucose levels and insulin tolerance testing.
Conclusions—These data demonstrate an important role for aP2 expression in the advanced stages of atherosclerotic lesion formation. Thus, aP2 provides an important physiological link between different features of the metabolic syndrome and is a potential target for therapy of atherosclerosis.
Key words: fatty acid
binding protein •
aP2 •
atherosclerosis •
mice •
insulin resistance
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