Metabolic implications of reduced heart-type fatty acid binding protein in insulin resistant cardiac muscle

Jane Shearer, Patrick T. Fueger, Zhi Zhang Wang, Deanna P. Bracy, David H. Wasserman, Jeffrey N. Rottman

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Insulin resistance is characterized by elevated rates of cardiac fatty acid utilization resulting in reduced efficiency and cardiomyopathy. One potential therapeutic approach is to limit the uptake and oxidation of fatty acids. The aims of this study were to determine whether a quantitative reduction in heart-type fatty acid binding protein (FABP3) normalizes cardiac substrate utilization without altering cardiac function. Transgenic (FABP3+/-) and wild-type (WT) littermates were studied following low fat (LF) or high fat (HF) diets, with HF resulting in obese, insulin-resistant mice. Cardiovascular function (systolic blood pressure, % fractional shortening) and heart dimension were measured at weaning and every month afterward for 3 mo. During this period cardiovascular function was the same independent of genotype and diet. Catheters were surgically implanted in the carotid artery and jugular vein for sampling and infusions in mice at 4 mo of age. Following 5 d recovery, mice underwent either a saline infusion or a hyperinsulinemic-euglycemic clamp (4 mU kg- 1 min- 1). Indices of long chain fatty acid and glucose utilization (Rf, Rg; μmol g wet weight- 1 min- 1) were obtained using 2-deoxy[3H]glucose and [125I]-15-ρ-iodophenyl)-3-R,S-methylpentadecanoic acid. FABP3+/- had enhanced cardiac Rg compared with WT during saline infusion in both LF and HF. FABP3+/- abrogated the HF-induced decrement in insulin-stimulated cardiac Rg. On a HF diet, FABP+/- but not WT had an increased reliance on fatty acids (Rf) during insulin stimulation. In conclusion, cardiac insulin resistance and glucose uptake is largely corrected by a reduction in FABP3 in vivo without contemporaneous deleterious effects on cardiac function.

Original languageEnglish (US)
Pages (from-to)586-592
Number of pages7
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1782
Issue number10
DOIs
StatePublished - Oct 1 2008

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Keywords

  • Fatty acid
  • Glucose
  • Hyperinsulinemic-euglycemic clamp
  • Obesity

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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