title: Partial gene deletion of heart-type fatty acid-binding protein limits the severity of dietary-induced insulin resistance.
abstract: The aim of this study was to determine the contribution of heart-type fatty acid-binding protein (H-FABP) to glucose and long-chain fatty acid (LCFA) utilization in dietary-induced insulin resistance. We tested the hypothesis that H-FABP facilitates increases in LCFA flux present in glucose-intolerant states and that a partial reduction in the amount of this protein would compensate for all or part of the impairment. Transgenic H-FABP heterozygotes (HET) and wild-type (WT) littermates were studied following chow diet (CHD) or high-fat diet (HFD) for 12 weeks. Catheters were surgically implanted in the carotid artery and jugular vein for sampling and infusions, respectively. Following 5 days of recovery, mice received either a saline infusion or underwent a euglycemic insulin clamp (4 mU x kg(-1) x min(-1)) for 120 min. At 90 min, a bolus of 2-deoxyglucose and [125I]-15-(rho-iodophenyl)-3-R,S-methylpentadecanoic acid were administered to obtain indexes of glucose and LCFA utilization. At 120 min, skeletal muscles were excised for tracer determination. All HFD mice were obese and hyperinsulinemic; however, only HFD-WT mice were hyperglycemic. Glucose infusion rates during insulin clamps were 49 +/- 4, 59 +/- 4, 16 +/- 4, and 33 +/- 4 mg x kg(-1) x min(-1) for CHD-WT, CHD-HET, HFD-WT, and HFD-HET mice, respectively, showing that HET limited the severity of whole-body insulin resistance with HFD. Insulin-stimulated muscle glucose utilization was attenuated in HFD-WT but unaffected in HFD-HET mice. Conversely, rates of LCFA clearance were increased with HFD feeding in HFD-WT but not in HFD-HET mice. In conclusion, a partial reduction in H-FABP protein normalizes fasting glucose levels and improves whole-body insulin sensitivity in HFD-fed mice despite obesity.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. jshearer@ucalgary.ca
authors.forename: Jane
authors.initials: J
authors.lastname: Shearer
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Fueger
authors.forename: Deanna P
authors.initials: DP
authors.lastname: Bracy
authors.forename: David H
authors.initials: DH
authors.lastname: Wasserman
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Rottman
mesh_terms: D000818:Animals; D001786:Blood Glucose; D002874:Chromosome Mapping; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins / Q000172:deficiency / Q000235:genetics*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics* / Q000502:physiology*; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D017384:Sequence Deletion / Q000235:genetics*
chemical_list: D001786:Blood Glucose; C493409:Fabp3 protein, mouse; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D005947:Glucose