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 Citations (Scopus)

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 2005
Externally publishedYes

Fingerprint

Fatty Acid-Binding Proteins
Gene Deletion
High Fat Diet
Insulin Resistance
Heterozygote
Glucose
Fatty Acids
Obese Mice
Insulin
Diet
Glucose Clamp Technique
Jugular Veins
Deoxyglucose
Carotid Arteries
Fasting
Skeletal Muscle
Proteins
Catheters
Obesity

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Partial gene deletion of heart-type fatty acid-binding protein limits the severity of dietary-induced insulin resistance. / Shearer, Jane; Fueger, Patrick T.; Bracy, Deanna P.; Wasserman, David H.; Rottman, Jeffrey N.

In: Diabetes, Vol. 54, No. 11, 11.2005, p. 3133-3139.

Research output: Contribution to journalArticle

Shearer, Jane ; Fueger, Patrick T. ; Bracy, Deanna P. ; Wasserman, David H. ; Rottman, Jeffrey N. / Partial gene deletion of heart-type fatty acid-binding protein limits the severity of dietary-induced insulin resistance. In: Diabetes. 2005 ; Vol. 54, No. 11. pp. 3133-3139.
@article{cbfce2d84ae94cca881392c41a29c576,
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·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.",
author = "Jane Shearer and Fueger, {Patrick T.} and Bracy, {Deanna P.} and Wasserman, {David H.} and Rottman, {Jeffrey N.}",
year = "2005",
month = "11",
doi = "10.2337/diabetes.54.11.3133",
language = "English (US)",
volume = "54",
pages = "3133--3139",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "11",

}

TY - JOUR

T1 - Partial gene deletion of heart-type fatty acid-binding protein limits the severity of dietary-induced insulin resistance

AU - Shearer, Jane

AU - Fueger, Patrick T.

AU - Bracy, Deanna P.

AU - Wasserman, David H.

AU - Rottman, Jeffrey N.

PY - 2005/11

Y1 - 2005/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33644666072&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33644666072&partnerID=8YFLogxK

U2 - 10.2337/diabetes.54.11.3133

DO - 10.2337/diabetes.54.11.3133

M3 - Article

C2 - 16249436

AN - SCOPUS:33644666072

VL - 54

SP - 3133

EP - 3139

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 11

ER -