Andre Sadler
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Last active: 11/15/2012

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

Shearer J, Fueger PT, Wang Z, Bracy DP, Wasserman DH, Rottman JN
Biochim Biophys Acta. 2008 1782 (10): 586-92

PMID: 18692568 · DOI:10.1016/j.bbadis.2008.07.003

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 (R(f), R(g); mumol g wet weight(-1) min(-1)) were obtained using 2-deoxy[(3)H]glucose and [(125)I]-15-rho-iodophenyl)-3-R,S-methylpentadecanoic acid. FABP3(+/-) had enhanced cardiac R(g) compared with WT during saline infusion in both LF and HF. FABP3(+/-) abrogated the HF-induced decrement in insulin-stimulated cardiac R(g). On a HF diet, FABP(+/-) but not WT had an increased reliance on fatty acids (R(f)) 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.

MeSH Terms (22)

Animals Blood Glucose Blood Pressure Body Weight Diet, Fat-Restricted Dietary Fats Fatty Acid-Binding Proteins Fatty Acid Binding Protein 3 Fatty Acids, Nonesterified Female Glucose Clamp Technique Heart Insulin Insulin Resistance Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Inbred Strains Mice, Transgenic Myocardium Ventricular Function

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