Requirement for the heart-type fatty acid binding protein in cardiac fattyacid utilization

Nonenzymatic cytosolic fatty acid binding proteins (FABPs) are abundantly e xpressed in many animal tissues with high rates of fatty acid metabolism. N o physiological role has been demonstrated for any FABP, although these pro teins have been implicated in transport of free long-chain fatty acids (LCF As) and protection against LCFA toxicity, We report here that mice lacking heart-type FABP (H-FABP) exhibit a severe defect of peripheral (nonhepatic, non-fat) LCFA utilization, In these mice, the heart is unable to efficient ly take up plasma LCFAs, which are normally its main fuel, and switches to glucose usage, Altered plasma levels of LCFAs, glucose, lactate and beta-hy droxybutyrate are consistent with depressed peripheral LCFA utilization, in tensified carbohydrate usage, and increased hepatic LCFA oxidation; these c hanges are most pronounced under conditions favoring LCFA oxidation. H-FABP deficiency is only incompletely compensated, however, causing acute exerci se intolerance and, at old age, a localized cardiac hypertrophy. These data establish a requirement for H-FABP in cardiac intracellular lipid transpor t and fuel selection and a major role in metabolic homeostasis. This new an imal model should be particularly useful for investigating the significance of peripheral LCFA utilization for heart function, insulin sensitivity, an d blood pressure.