Adipocyte fatty acid-binding protein, aP2, alters late atherosclerotic lesion formation in severe hypercholesterolemia.
OBJECTIVE
The adipocyte fatty acid-binding 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.


RESULTS
Mice deficient in aP2 and apolipoprotein E (aP2(-/-)apoE(-/-) mice) and apolipoprotein E-deficient 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.
Boord
Jeffrey B
JB
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn, USA.
Maeda
Kazuhisa
K
Makowski
Liza
L
Babaev
Vladimir R
VR
Fazio
Sergio
S
Linton
MacRae F
MF
Hotamisligil
Gökhan S
GS
D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001161:Arteriosclerosis / Q000235:genetics / Q000503:physiopathology*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005260:Female; D006937:Hypercholesterolemia / Q000503:physiopathology*; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008817:Mice, Mutant Strains; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins
D001057:Apolipoproteins E; D002352:Carrier Proteins; C082667:Fabp5 protein, mouse; C086936:Fabp7 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins