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This Article Full Text Full Text (PDF) All Versions of this Article: 288/2/E292    most recent 00287.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Shearer, J. Articles by Wasserman, D. H. Search for Related Content PubMed PubMed Citation Articles by Shearer, J. Articles by Wasserman, D. H.

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

Departments of ¹Molecular Physiology and Biophysics, ²Cardiology, and ³Mouse Metabolic Phenotyping Center, Vanderbilt University, Nashville, Tennessee; ⁴Department of Pathobiology, College of Veterinary Medicine, Texas A & M University, College Station, Texas

Submitted 1 July 2004 ; accepted in final form 23 September 2004

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 [¹²⁵I]-15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid and 2-deoxy-[³H]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.

skeletal muscle; metabolism; substrate balance; 2-deoxyglucose; 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid

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