Impaired long-chain fatty acid utilization by cardiac myocytes isolated from mice lacking the heart-type fatty acid binding protein gene.
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.
Schaap
F G
FG
Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, the Netherlands. Germany.
Binas
B
B
Danneberg
H
H
van der Vusse
G J
GJ
Glatz
J F
JF
D000818:Animals; D001692:Biological Transport / Q000235:genetics; D002352:Carrier Proteins / Q000502:physiology*; D004734:Energy Metabolism; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000502:physiology*; D006321:Heart / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D018996:Myelin P2 Protein / Q000502:physiology*; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D010084:Oxidation-Reduction
D002352:Carrier Proteins; C082667:Fabp5 protein, mouse; C086936:Fabp7 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D018996:Myelin P2 Protein; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins