© 1999 American Heart Association, Inc.
Cellular Biology |
Impaired Long-Chain Fatty Acid Utilization by Cardiac Myocytes Isolated From Mice Lacking the Heart-Type Fatty Acid Binding Protein Gene
From the Department of Physiology (F.G.S., G.J.v.d.V., J.F.C.G.), Cardiovascular Research Institute Maastricht, Maastricht University, the Netherlands, and Hypertension Research (B.B., H.D.), Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany.
Correspondence to Dr J.F.C. Glatz, Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Universiteitssingel 50, PO Box 616, 6200 MD Maastricht, the Netherlands. E-mail glatz{at}fys.unimaas.nl
Abstract—Heart-type fatty acid binding protein (H-FABP), abundantly expressed in cardiac myocytes, has been postulated to facilitate the cardiac uptake of long-chain fatty acids (LCFAs) and to promote their intracellular trafficking to sites of metabolic conversion. Mice with a disrupted H-FABP gene were recently shown to have elevated plasma LCFA levels, decreased cardiac deposition of a LCFA analogue, and increased cardiac deoxyglucose uptake, which qualitatively establishes a requirement for H-FABP in cardiac LCFA utilization. To study the underlying defect, we developed a method to isolate intact, electrically stimulatable cardiac myocytes from adult mice and then studied substrate utilization under defined conditions in quiescent and in contracting cells from wild-type and H-FABP-/- mice. Our results demonstrate that in resting and in contracting myocytes from H-FABP-/- mice, both uptake and oxidation of palmitate are markedly reduced (between –45% and –65%), whereas cellular octanoate uptake, and the capacities of heart homogenates for palmitate oxidation and for octanoate oxidation, and the cardiac levels of mRNAs encoding sarcolemmal FA transporters remain unaltered. In contrast, in resting H-FABP-/- cardiac myocytes, glucose oxidation is increased (+80%) to a level that would require electrical stimulation in wild-type cells. These findings provide a physiological demonstration of a crucial role of H-FABP in uptake and oxidation of LCFAs in cardiac muscle cells and indicate that in H-FABP-/- mice the diminished contribution of LCFAs to cardiac energy production is, at least in part, compensated for by an increase in glucose oxidation.
Key Words: myocardium • isolated cardiac myocyte • fatty acid binding protein • fatty acid transport • metabolism
This article has been cited by other articles:
 |
|
 |
|
  L. L. Y. Chan, S. P. Sebert, M. A. Hyatt, T. Stephenson, H. Budge, M. E. Symonds, and D. S. Gardner Effect of maternal nutrient restriction from early to midgestation on cardiac function and metabolism after adolescent-onset obesity Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2009; 296(5): R1455 - R1463. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-Y. Chen, B.-C. Lee, H.-C. Hsu, H.-J. Lin, C.-L. Chao, Y.-H. Lin, Y.-L. Ho, and M.-F. Chen A proteomic study of the effects of ramipril on post-infarction left ventricular remodelling in the rabbit Eur J Heart Fail, August 1, 2008; 10(8): 740 - 748. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. W. Schwenk, J. J.F.P. Luiken, A. Bonen, and J. F.C. Glatz Regulation of sarcolemmal glucose and fatty acid transporters in cardiac disease Cardiovasc Res, July 15, 2008; 79(2): 249 - 258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. C. Heather, M. A. Cole, C. A. Lygate, R. D. Evans, D. J. Stuckey, A. J. Murray, S. Neubauer, and K. Clarke Fatty acid transporter levels and palmitate oxidation rate correlate with ejection fraction in the infarcted rat heart Cardiovasc Res, December 1, 2006; 72(3): 430 - 437. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Hafstad, G. H. Solevag, D. L. Severson, T. S. Larsen, and E. Aasum Perfused hearts from Type 2 diabetic (db/db) mice show metabolic responsiveness to insulin Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1763 - H1769. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R.-S. Ge, Q. Dong, C. M. Sottas, H. Chen, B. R. Zirkin, and M. P. Hardy Gene Expression in Rat Leydig Cells During Development from the Progenitor to Adult Stage: A Cluster Analysis Biol Reprod, June 1, 2005; 72(6): 1405 - 1415. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Noushmehr, E. D'Amico, L. Farilla, H. Hui, K. A. Wawrowsky, W. Mlynarski, A. Doria, N. A. Abumrad, and R. Perfetti Fatty Acid Translocase (FAT/CD36) Is Localized on Insulin-Containing Granules in Human Pancreatic {beta}-Cells and Mediates Fatty Acid Effects on Insulin Secretion Diabetes, February 1, 2005; 54(2): 472 - 481. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Shearer, P. T. Fueger, J. N. Rottman, D. P. Bracy, B. Binas, and D. H. Wasserman Heart-type fatty acid-binding protein reciprocally regulates glucose and fatty acid utilization during exercise Am J Physiol Endocrinol Metab, February 1, 2005; 288(2): E292 - E297. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. W. Castellani, P. Gargalovic, M. Febbraio, S. Charugundla, M.-L. Jien, and A. J. Lusis Mechanisms mediating insulin resistance in transgenic mice overexpressing mouse apolipoprotein A-II J. Lipid Res., December 1, 2004; 45(12): 2377 - 2387. [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]
|
|
|
|
 |
|
 E. J. Murphy, G. Barcelo-Coblijn, B. Binas, and J. F. C. Glatz Heart Fatty Acid Uptake Is Decreased in Heart Fatty Acid-binding Protein Gene-ablated Mice J. Biol. Chem., August 13, 2004; 279(33): 34481 - 34488. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Binas, X.-X. Han, E. Erol, J. J. F. P. Luiken, J. F. C. Glatz, D. J. Dyck, R. Motazavi, P. J. Adihetty, D. A. Hood, and A. Bonen A null mutation in H-FABP only partially inhibits skeletal muscle fatty acid metabolism Am J Physiol Endocrinol Metab, September 1, 2003; 285(3): E481 - E489. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Christoffersen, E. Bollano, M. L. S. Lindegaard, E. D. Bartels, J. P. Goetze, C. B. Andersen, and L. B. Nielsen Cardiac Lipid Accumulation Associated with Diastolic Dysfunction in Obese Mice Endocrinology, August 1, 2003; 144(8): 3483 - 3490. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Irie, I. B. Krukenkamp, J. F. F. Brinkmann, G. R. Gaudette, A. E. Saltman, W. Jou, J. F. C. Glatz, N. A. Abumrad, and A. Ibrahimi Myocardial recovery from ischemia is impaired in CD36-null mice and restored by myocyte CD36 expression or medium-chain fatty acids PNAS, May 27, 2003; 100(11): 6819 - 6824. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. van Rooij, P. A. Doevendans, C. C. de Theije, F. A. Babiker, J. D. Molkentin, and L. J. De Windt Requirement of Nuclear Factor of Activated T-cells in Calcineurin-mediated Cardiomyocyte Hypertrophy J. Biol. Chem., December 6, 2002; 277(50): 48617 - 48626. [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]
|
|
|
|
 |
|
 B. P. Atshaves, S. M. Storey, A. Petrescu, C. C. Greenberg, O. I. Lyuksyutova, R. Smith III, and F. Schroeder Expression of fatty acid binding proteins inhibits lipid accumulation and alters toxicity in L cell fibroblasts Am J Physiol Cell Physiol, September 1, 2002; 283(3): C688 - C703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. F. P. Luiken, Y. Arumugam, R. C. Bell, J. Calles-Escandon, N. N. Tandon, J. F. C. Glatz, and A. Bonen Changes in fatty acid transport and transporters are related to the severity of insulin deficiency Am J Physiol Endocrinol Metab, September 1, 2002; 283(3): E612 - E621. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J van der Vusse, M. van Bilsen, and J. F.C Glatz Cardiac fatty acid uptake and transport in health and disease Cardiovasc Res, January 14, 2000; 45(2): 279 - 293. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. F. P. Luiken, Y. Arumugam, D. J. Dyck, R. C. Bell, M. M. L. Pelsers, L. P. Turcotte, N. N. Tandon, J. F. C. Glatz, and A. Bonen Increased Rates of Fatty Acid Uptake and Plasmalemmal Fatty Acid Transporters in Obese Zucker Rats J. Biol. Chem., October 26, 2001; 276(44): 40567 - 40573. [Abstract] [Full Text] [PDF]
|
|