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

Jane Shearer, Patrick T. Fueger, Jeffrey N. Rottman, Deanna P. Bracy, Bert Binas, David H. Wasserman

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

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 (Rf) and glucose (Rg) 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 Rf and increasing Rg 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.

Original languageEnglish (US)
Pages (from-to)E292-E297
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume288
Issue number2 51-2
DOIs
StatePublished - Feb 2005

Keywords

  • 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid
  • 2-deoxyglucose
  • Metabolism
  • Skeletal muscle
  • Substrate balance

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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