Heart-type fatty acid-binding protein reciprocally regulates glucose and fatty acid utilization during exercise

The role of heart-type cytosolic fatty acid-binding protein (H-FABP) in mediating whole body and muscle-specific long-chain fatty acid (LCFA) and glucose utilization was examined using exercise as a phenotyping tool. Catheters were chronically implanted in a carotid artery and jugular vein of wild-type (WT, n = 8), heterozygous (H-FABP(+/-), n = 8), and null (H-FABP(-/-), n = 7) chow-fed C57BL/6J mice, and mice were allowed to recover for 7 days. After a 5-h fast, conscious, unrestrained mice were studied during 30 min of treadmill exercise (0.6 mph). A bolus of [I-125]-15( p-iodophenyl)-3-R, S- methylpentadecanoic acid and 2-deoxy[ H-3] glucose was administered to obtain rates of whole body metabolic clearance (MCR) and indexes of muscle LCFA (R-f) and glucose (R-g) utilization. Fasting, nonesterified fatty acids (mM) were elevated in H- FABP(-/-) mice (2.2 +/- 0.9 vs. 1.3 +/- 0.1 and 1.3 +/- 0.2 for WT and H- FABP(+/-)). During exercise, blood glucose (mM) increased in WT (11.7 +/- 0.8) and H-FABP(+/-) (12.6 +/- 0.9) mice, whereas H- FABP(-/-) mice developed overt hypoglycemia (4.8 +/- 0.8). Examination of tissue- specific and whole body glucose and LCFA utilization demonstrated a dependency on H- FABP with exercise in all tissues examined. Reductions in H- FABP led to decreasing exercise-stimulated R-f and increasing R-g with the most pronounced effects in heart and soleus muscle. Similar results were seen for MCR with decreasing LCFA and increasing glucose clearance with declining levels of H- FABP. These results show that, in vivo, H- FABP has reciprocal effects on glucose and LCFA utilization and whole body fuel homeostasis when metabolic demands are elevated by exercise.