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 car diac myocytes, has been postulated to facilitate the cardiac uptake of long -chain fatty acids (LCFAs) and to promote their intracellular trafficking t o sites of metabolic conversion. Mice with a disrupted H-FABP gene were rec ently shown to have elevated plasma LCFA levels, decreased cardiac depositi on of a LCFA analogue, and increased cardiac deoxyglucose uptake, which qua litatively 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 contrac ting cells from wild-type and H-FABP(-/-) mice. Our results demonstrate tha t in resting and in contracting myocytes from H-FABP(-/-) mice, both uptake and oxidation of palmitate are markedly reduced (between -45% and -65%), w hereas cellular octanoate uptake, and the capacities of heart homogenates f or 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 cel ls. These findings provide a physiological demonstration of a crucial role of H-FABP in uptake and oxidation of LCFAs in cardiac muscle cells and indi cate that in H-FABP(-/-) mice the diminished contribution of LCFAs to cardi ac energy production is, at least in part, compensated for by an increase i n glucose oxidation.