| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
ARTICLES |
Division of Biological Sciences and Department of Nutrition (K.T.U., L.S., S.M.W., G.S.H.), Harvard School of Public Health, Boston, Massachusetts 02115; and Research Division (S.B.W.), Joslin Diabetes Center, Boston, Massachusetts 02215
Address all correspondence and requests for reprints to: Gökhan S. Hotamisligil, M.D., Ph.D., Harvard School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115. E-mail: ghotamis{at}hsph.harvard.edu
Adipocyte fatty acid-binding protein, aP2, is a member of the intracellular fatty acid binding protein family. Previously, studies have shown increased insulin sensitivity in aP2-deficient mice with dietary obesity. Here, we asked whether aP2-related alterations in lipolytic response and insulin production are features of obesity-induced insulin resistance and investigated the effects of aP2-deficiency on glucose homeostasis and lipid metabolism in ob/ob mice, a model of extreme obesity. ob/ob mice homozygous for the aP2 null allele (ob/ob-aP2-/-) became more obese than ob/ob mice as indicated by significantly increased body weight and fat pad size but unaltered body length. However, despite their extreme adiposity, ob/ob-aP2-/- animals were more insulin-sensitive compared with ob/ob controls, as demonstrated by significantly lower plasma glucose and insulin levels and better performance in both insulin and glucose tolerance tests. These animals also showed improvements in dyslipidemia and had lower plasma triglyceride and cholesterol levels. Lipolytic response to ß-adrenergic stimulation and lipolysis-associated insulin secretion was significantly reduced in ob/ob-aP2-/- mice. Interestingly, glucose-stimulated insulin secretion, while virtually abolished in ob/ob controls, was significantly improved in ob/ob-aP2-/- animals. There were no apparent morphological differences in the structure or size of the pancreatic islets between genotypes. Taken together, the data indicate that in obesity, aP2-deficiency not only improves peripheral insulin resistance but also preserves pancreatic ß cell function and has beneficial effects on lipid metabolism.
This article has been cited by other articles:
 |
|
 |
|
  S. Kralisch, H. Stepan, J. Kratzsch, M. Verlohren, H.-J. Verlohren, K. Drynda, U. Lossner, M. Bluher, M. Stumvoll, and M. Fasshauer Serum levels of adipocyte fatty acid binding protein are increased in gestational diabetes mellitus Eur. J. Endocrinol., January 1, 2009; 160(1): 33 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Hyun Koh, Y. Goo Shin, S. Min Nam, M. Young Lee, C. Hee Chung, and J. Yel Shin Serum Adipocyte Fatty Acid-Binding Protein Levels Are Associated With Nonalcoholic Fatty Liver Disease in Type 2 Diabetic Patients Diabetes Care, January 1, 2009; 32(1): 147 - 152. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 P. W. Franks, C. Scheele, R. J. F. Loos, A. R. Nielsen, F. M. Finucane, C. Wahlestedt, B. K. Pedersen, N. J. Wareham, and J. A. Timmons Genomic variants at the PINK1 locus are associated with transcript abundance and plasma nonesterified fatty acid concentrations in European whites FASEB J, September 1, 2008; 22(9): 3135 - 3145. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Paterson, I. R Kelsall, and P. T W Cohen Disruption of the striated muscle glycogen-targeting subunit of protein phosphatase 1: influence of the genetic background J. Mol. Endocrinol., February 1, 2008; 40(2): 47 - 59. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. W.K. Tso, A. Xu, P. C. Sham, N. M.S. Wat, Y. Wang, C. H.Y. Fong, B. M.Y. Cheung, E. D. Janus, and K. S.L. Lam Serum Adipocyte Fatty Acid Binding Protein as a New Biomarker Predicting the Development of Type 2 Diabetes: A 10-year prospective study in a Chinese cohort Diabetes Care, October 1, 2007; 30(10): 2667 - 2672. [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]
|
|
|
|
 |
|
 A. Xu, A. W.K. Tso, B. M.Y. Cheung, Y. Wang, N. M.S. Wat, C. H.Y. Fong, D. C.Y. Yeung, E. D. Janus, P. C. Sham, and K. S.L. Lam Circulating Adipocyte-Fatty Acid Binding Protein Levels Predict the Development of the Metabolic Syndrome: A 5-Year Prospective Study Circulation, March 27, 2007; 115(12): 1537 - 1543. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Rolph, T. R. Young, B. O. V. Shum, C. Z. Gorgun, C. Schmitz-Peiffer, I. A. Ramshaw, G. S. Hotamisligil, and C. R. Mackay Regulation of Dendritic Cell Function and T Cell Priming by the Fatty Acid-Binding Protein aP2 J. Immunol., December 1, 2006; 177(11): 7794 - 7801. [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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 A. Xu, Y. Wang, J. Y. Xu, D. Stejskal, S. Tam, J. Zhang, N. M.S. Wat, W. K. Wong, and K. S.L. Lam Adipocyte Fatty Acid-Binding Protein Is a Plasma Biomarker Closely Associated with Obesity and Metabolic Syndrome Clin. Chem., March 1, 2006; 52(3): 405 - 413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Timmons, O. Larsson, E. Jansson, H. Fischer, T. Gustafsson, P. L. Greenhaff, J. Ridden, J. Rachman, M. Peyrard-Janvid, C. Wahlestedt, et al. Human muscle gene expression responses to endurance training provide a novel perspective on Duchenne muscular dystrophy FASEB J, May 1, 2005; 19(7): 750 - 760. [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]
|
|
|
|
|
|
R. A. Baar, C. S. Dingfelder, L. A. Smith, D. A. Bernlohr, C. Wu, A. J. Lange, and E. J. Parks Investigation of in vivo fatty acid metabolism in AFABP/aP2-/- mice Am J Physiol Endocrinol Metab, January 1, 2005; 288(1): E187 - E193. [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]
|
|
|
|
|
|
M. Bluher, L. Wilson-Fritch, J. Leszyk, P. G. Laustsen, S. Corvera, and C. R. Kahn Role of Insulin Action and Cell Size on Protein Expression Patterns in Adipocytes J. Biol. Chem., July 23, 2004; 279(30): 31902 - 31909. [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]
|
|
|
|
 |
|
 P. Dandona, A. Aljada, A. Chaudhuri, and A. Bandyopadhyay The Potential Influence of Inflammation and Insulin Resistance on the Pathogenesis and Treatment of Atherosclerosis-Related Complications in Type 2 Diabetes J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2422 - 2429. [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]
|
|
|
|
 |
|
 S. Lucas, G. Tavernier, C. Tiraby, A. Mairal, and D. Langin Expression of human hormone-sensitive lipase in white adipose tissue of transgenic mice increases lipase activity but does not enhance in vitro lipolysis J. Lipid Res., January 1, 2003; 44(1): 154 - 163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. V. Hertzel, A. Bennaars-Eiden, and D. A. Bernlohr Increased lipolysis in transgenic animals overexpressing the epithelial fatty acid binding protein in adipose cells J. Lipid Res., December 1, 2002; 43(12): 2105 - 2111. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B. Boord, K. Maeda, L. Makowski, V. R. Babaev, S. Fazio, M. F. Linton, and G. S. Hotamisligil Adipocyte Fatty Acid-Binding Protein, aP2, Alters Late Atherosclerotic Lesion Formation in Severe Hypercholesterolemia Arterioscler. Thromb. Vasc. Biol., October 1, 2002; 22(10): 1686 - 1691. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Valet, G. Tavernier, I. Castan-Laurell, J. S. Saulnier-Blache, and D. Langin Understanding adipose tissue development from transgenic animal models J. Lipid Res., June 1, 2002; 43(6): 835 - 860. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Rosenzweig, L. Braiman, A. Bak, A. Alt, T. Kuroki, and S. R. Sampson Differential Effects of Tumor Necrosis Factor-{alpha} on Protein Kinase C Isoforms {alpha} and {delta} Mediate Inhibition of Insulin Receptor Signaling Diabetes, June 1, 2002; 51(6): 1921 - 1930. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. F. Lewis, A. Carpentier, K. Adeli, and A. Giacca Disordered Fat Storage and Mobilization in the Pathogenesis of Insulin Resistance and Type 2 Diabetes Endocr. Rev., April 1, 2002; 23(2): 201 - 229. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Guerre-Millo, C. Rouault, P. Poulain, J. Andre, V. Poitout, J. M. Peters, F. J. Gonzalez, J.-C. Fruchart, G. Reach, and B. Staels PPAR-{alpha}-Null Mice Are Protected From High-Fat Diet-Induced Insulin Resistance Diabetes, December 1, 2001; 50(12): 2809 - 2814. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
