Published online before print August 8, 2002, doi: 10.1161/01.ATV.0000033090.81345.E6
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2002 American Heart Association, Inc.
Atherosclerosis |
Adipocyte Fatty Acid–Binding Protein, aP2, Alters Late Atherosclerotic Lesion Formation in Severe Hypercholesterolemia
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.
Correspondence to Gökhan S. Hotamisligil, Harvard School of Public Health, Division of Biological Sciences and Department of Nutrition, 665 Huntington Ave, Boston, MA 02115. E-mail ghotamis{at}hsph.harvard.edu or MacRae F. Linton, Vanderbilt University School of Medicine, 383 PRB, Nashville, TN 37232-6300. E-mail MacRae.Linton@vanderbilt.edu
Abstract
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.
Methods and 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.
Key Words: fatty acid–binding protein • aP2 • atherosclerosis • mice • insulin resistance
This article has been cited by other articles:
 |
|
 |
|
  D. C.Y. Yeung, Y. Wang, A. Xu, S. C.W. Cheung, N. M.S. Wat, D. Y.T. Fong, C. H.Y. Fong, M.T. Chau, P. C. Sham, and K. S.L. Lam Epidermal fatty-acid-binding protein: a new circulating biomarker associated with cardio-metabolic risk factors and carotid atherosclerosis Eur. Heart J., September 1, 2008; 29(17): 2156 - 2163. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D.C.Y. Yeung, A. Xu, C.W.S. Cheung, N.M.S. Wat, M.H. Yau, C.H.Y. Fong, M.T. Chau, and K.S.L. Lam Serum Adipocyte Fatty Acid-Binding Protein Levels Were Independently Associated With Carotid Atherosclerosis Arterioscler. Thromb. Vasc. Biol., August 1, 2007; 27(8): 1796 - 1802. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Wang, K. S. L. Lam, E. W. Kraegen, G. Sweeney, J. Zhang, A. W.K. Tso, W.-S. Chow, N. M.S. Wat, J. Y. Xu, R. L.C. Hoo, et al. Lipocalin-2 Is an Inflammatory Marker Closely Associated with Obesity, Insulin Resistance, and Hyperglycemia in Humans Clin. Chem., January 1, 2007; 53(1): 34 - 41. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Cao, K. Maeda, C. Z. Gorgun, H.-J. Kim, S.-Y. Park, G. I. Shulman, J. K. Kim, and G. S. Hotamisligil Regulation of metabolic responses by adipocyte/ macrophage Fatty Acid-binding proteins in leptin-deficient mice. Diabetes, July 1, 2006; 55(7): 1915 - 1922. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Jean-Louis, S. Akare, M. A. Ali, E. A. Mash Jr., E. Meuillet, and J. D. Martinez Deoxycholic Acid Induces Intracellular Signaling through Membrane Perturbations J. Biol. Chem., May 26, 2006; 281(21): 14948 - 14960. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Tuncman, E. Erbay, X. Hom, I. De Vivo, H. Campos, E. B. Rimm, and G. S. Hotamisligil A genetic variant at the fatty acid-binding protein aP2 locus reduces the risk for hypertriglyceridemia, type 2 diabetes, and cardiovascular disease PNAS, May 2, 2006; 103(18): 6970 - 6975. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. V. Hertzel, L. A. Smith, A. H. Berg, G. W. Cline, G. I. Shulman, P. E. Scherer, and D. A. Bernlohr Lipid metabolism and adipokine levels in fatty acid-binding protein null and transgenic mice Am J Physiol Endocrinol Metab, May 1, 2006; 290(5): E814 - E823. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Song, J. L. Barth, Y. Yu, K. Lu, A. Dashti, Y. Huang, C. K. Gittinger, W. S. Argraves, and T. J. Lyons Effects of Oxidized and Glycated LDL on Gene Expression in Human Retinal Capillary Pericytes Invest. Ophthalmol. Vis. Sci., August 1, 2005; 46(8): 2974 - 2982. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. K. Hansson and K. Edfeldt Toll To Be Paid at the Gateway to the Vessel Wall Arterioscler. Thromb. Vasc. Biol., June 1, 2005; 25(6): 1085 - 1087. [Full Text] [PDF]
|
|
|
|
|
|
M. R. Kazemi, C. M. McDonald, J. K. Shigenaga, C. Grunfeld, and K. R. Feingold Adipocyte Fatty Acid-Binding Protein Expression and Lipid Accumulation Are Increased During Activation of Murine Macrophages by Toll-Like Receptor Agonists Arterioscler. Thromb. Vasc. Biol., June 1, 2005; 25(6): 1220 - 1224. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Makowski, K. C. Brittingham, J. M. Reynolds, J. Suttles, and G. S. Hotamisligil The Fatty Acid-binding Protein, aP2, Coordinates Macrophage Cholesterol Trafficking and Inflammatory Activity: MACROPHAGE EXPRESSION OF aP2 IMPACTS PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR {gamma} AND I{kappa}B KINASE ACTIVITIES J. Biol. Chem., April 1, 2005; 280(13): 12888 - 12895. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Fach, L.-A. Garulacan, J. Gao, Q. Xiao, S. M. Storm, Y. P. Dubaquie, S. A. Hefta, and G. J. Opiteck In Vitro Biomarker Discovery for Atherosclerosis by Proteomics Mol. Cell. Proteomics, December 1, 2004; 3(12): 1200 - 1210. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. B. Boord, K. Maeda, L. Makowski, V. R. Babaev, S. Fazio, M. F. Linton, and G. S. Hotamisligil Combined Adipocyte-Macrophage Fatty Acid-Binding Protein Deficiency Improves Metabolism, Atherosclerosis, and Survival in Apolipoprotein E-Deficient Mice Circulation, September 14, 2004; 110(11): 1492 - 1498. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Makowski and G. S. Hotamisligil Fatty Acid Binding Proteins--The Evolutionary Crossroads of Inflammatory and Metabolic Responses J. Nutr., September 1, 2004; 134(9): 2464S - 2468S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Jenkins-Kruchten, A. Bennaars-Eiden, J. R. Ross, W.-J. Shen, F. B. Kraemer, and D. A. Bernlohr Fatty Acid-binding Protein-Hormone-sensitive Lipase Interaction: FATTY ACID DEPENDENCE ON BINDING J. Biol. Chem., November 28, 2003; 278(48): 47636 - 47643. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Maeda, K. T. Uysal, L. Makowski, C. Z. Gorgun, G. Atsumi, R. A. Parker, J. Bruning, A. V. Hertzel, D. A. Bernlohr, and G. S. Hotamisligil Role of the Fatty Acid Binding Protein mal1 in Obesity and Insulin Resistance Diabetes, February 1, 2003; 52(2): 300 - 307. [Abstract] [Full Text] [PDF]
|
|