Key result
In mice, reductions in H-FABP led to decreasing exercise-stimulated long-chain fatty acid utilization and increasing glucose utilization, with H-FABP null mice developing overt hypoglycemia.
H-FABP plays a critical role in regulating the reciprocal utilization of glucose and long-chain fatty acids during exercise, with its absence leading to exercise-induced hypoglycemia.
H-FABP loss impairs fatty acid use and triggers hypoglycemia during exercise in mice; hypothesis-generating for human substrate metabolism, no practice change.
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 [(125)I]-15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid and 2-deoxy-[(3)H]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.
No takes yet. Share an insight, caveat, or question.
Shearer et al. (2004) studied this question. H-FABP deficiency vs. Wild-type mice was evaluated on Blood glucose, nonesterified fatty acids, and rates of whole body metabolic clearance and muscle LCFA and glucose utilization. In mice, reductions in H-FABP led to decreasing exercise-stimulated long-chain fatty acid utilization and increasing glucose utilization, with H-FABP null mice developing overt hypoglycemia.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: