Partial gene deletion of heart-type fatty acid-binding protein limits the severity of dietary-induced insulin resistance

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

Research output: Contribution to journalArticle

31 Scopus citations

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·kg-1·min-1) for 120 min. At 90 min, a bolus of 2-deoxyglucose and [125I]-15- (ρ-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·kg-1·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.

Original languageEnglish (US)
Pages (from-to)3133-3139
Number of pages7
JournalDiabetes
Volume54
Issue number11
DOIs
StatePublished - Nov 1 2005

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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