Chronic ethanol-induced insulin resistance is associated with macrophage infiltration into adipose tissue and altered expression of adipocytokines

Li Kang, Becky M. Sebastian, Michele T. Pritchard, Brian T. Pratt, Stephen F. Previs, Laura E. Nagy

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

BACKGROUND: Chronic ethanol consumption disrupts glucose homeostasis and is associated with the development of insulin resistance. While adipose tissue and skeletal muscle are the two major organs utilizing glucose in response to insulin, the relative contribution of these two tissues to impaired glucose homeostasis during chronic ethanol feeding is not known. As other models of insulin resistance, such as obesity, are characterized by an infiltration of macrophages into adipose tissue, as well as changes in the expression of adipocytokines that play a central role in the regulation of insulin sensitivity, we hypothesized that chronic ethanol-induced insulin resistance would be associated with increased macrophage infiltration into adipose tissue and changes in the expression of adipocytokines by adipose tissue.

METHODS: Male Wistar rats were fed a liquid diet containing ethanol as 36% of calories or pair-fed a control diet for 4 weeks. The effects of chronic ethanol feeding on insulin-stimulated glucose utilization were studied using the hyperinsulinemic-euglycemic clamp technique, coupled with the use of isotopic tracers. Further, macrophage infiltration into adipose tissue and expression of adipocytokines were also assessed after chronic ethanol feeding.

RESULTS: Hyperinsulinemic-euglycemic clamp studies revealed that chronic ethanol feeding to rats decreased whole-body glucose utilization and decreased insulin-mediated suppression of hepatic glucose production. Chronic ethanol feeding decreased glucose uptake in epididymal, subcutaneous, and omental adipose tissue during the hyperinsulinemic-euglycemic clamp, but had no effect on glucose disposal in skeletal muscle. Chronic ethanol feeding increased the infiltration of macrophages into epididymal adipose tissue and changed the expression of mRNA for adipocytokines: expression of mRNA for monocyte chemoattractant protein 1, tumor necrosis factor alpha, and interleukin-6 were increased, while expression of mRNA for retinol binding protein 4 and adiponectin were decreased in epididymal adipose tissue.

CONCLUSIONS: These data demonstrate that chronic ethanol feeding results in the development of insulin resistance, associated with impaired insulin-mediated suppression of hepatic glucose production and decreased insulin-stimulated glucose uptake into adipose tissue. Chronic ethanol-induced insulin resistance was associated with increased macrophage infiltration into adipose tissue, as well as changes in the expression of adipocytokines by adipose tissue.

Original languageEnglish
Pages (from-to)1581-8
Number of pages8
JournalAlcoholism: Clinical and Experimental Research
Volume31
Issue number9
DOIs
Publication statusPublished - 11 Jul 2007

Fingerprint

Adipokines
Macrophages
Infiltration
Insulin Resistance
Adipose Tissue
Ethanol
Insulin
Tissue
Glucose
Glucose Clamp Technique
Clamping devices
Nutrition
Messenger RNA
Skeletal Muscle
Muscle
Homeostasis
Rats
Diet
Retinol-Binding Proteins
Chemokine CCL2

Keywords

  • Adiponectin/metabolism
  • Adipose Tissue/drug effects
  • Alcoholism/metabolism
  • Animals
  • Cell Movement/drug effects
  • Central Nervous System Depressants/adverse effects
  • Chemokine CCL2/metabolism
  • Cytokines/metabolism
  • Disease Models, Animal
  • Ethanol/adverse effects
  • Glucose/metabolism
  • Glucose Clamp Technique
  • Insulin Resistance/physiology
  • Interleukin-6/metabolism
  • Macrophages/drug effects
  • Male
  • Muscle, Skeletal/metabolism
  • Rats
  • Rats, Wistar
  • Retinol-Binding Proteins/metabolism
  • Retinol-Binding Proteins, Plasma
  • Tumor Necrosis Factor-alpha/metabolism

Cite this

Kang, Li ; Sebastian, Becky M. ; Pritchard, Michele T. ; Pratt, Brian T. ; Previs, Stephen F. ; Nagy, Laura E. / Chronic ethanol-induced insulin resistance is associated with macrophage infiltration into adipose tissue and altered expression of adipocytokines. In: Alcoholism: Clinical and Experimental Research. 2007 ; Vol. 31, No. 9. pp. 1581-8.
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abstract = "BACKGROUND: Chronic ethanol consumption disrupts glucose homeostasis and is associated with the development of insulin resistance. While adipose tissue and skeletal muscle are the two major organs utilizing glucose in response to insulin, the relative contribution of these two tissues to impaired glucose homeostasis during chronic ethanol feeding is not known. As other models of insulin resistance, such as obesity, are characterized by an infiltration of macrophages into adipose tissue, as well as changes in the expression of adipocytokines that play a central role in the regulation of insulin sensitivity, we hypothesized that chronic ethanol-induced insulin resistance would be associated with increased macrophage infiltration into adipose tissue and changes in the expression of adipocytokines by adipose tissue.METHODS: Male Wistar rats were fed a liquid diet containing ethanol as 36{\%} of calories or pair-fed a control diet for 4 weeks. The effects of chronic ethanol feeding on insulin-stimulated glucose utilization were studied using the hyperinsulinemic-euglycemic clamp technique, coupled with the use of isotopic tracers. Further, macrophage infiltration into adipose tissue and expression of adipocytokines were also assessed after chronic ethanol feeding.RESULTS: Hyperinsulinemic-euglycemic clamp studies revealed that chronic ethanol feeding to rats decreased whole-body glucose utilization and decreased insulin-mediated suppression of hepatic glucose production. Chronic ethanol feeding decreased glucose uptake in epididymal, subcutaneous, and omental adipose tissue during the hyperinsulinemic-euglycemic clamp, but had no effect on glucose disposal in skeletal muscle. Chronic ethanol feeding increased the infiltration of macrophages into epididymal adipose tissue and changed the expression of mRNA for adipocytokines: expression of mRNA for monocyte chemoattractant protein 1, tumor necrosis factor alpha, and interleukin-6 were increased, while expression of mRNA for retinol binding protein 4 and adiponectin were decreased in epididymal adipose tissue.CONCLUSIONS: These data demonstrate that chronic ethanol feeding results in the development of insulin resistance, associated with impaired insulin-mediated suppression of hepatic glucose production and decreased insulin-stimulated glucose uptake into adipose tissue. Chronic ethanol-induced insulin resistance was associated with increased macrophage infiltration into adipose tissue, as well as changes in the expression of adipocytokines by adipose tissue.",
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author = "Li Kang and Sebastian, {Becky M.} and Pritchard, {Michele T.} and Pratt, {Brian T.} and Previs, {Stephen F.} and Nagy, {Laura E.}",
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Chronic ethanol-induced insulin resistance is associated with macrophage infiltration into adipose tissue and altered expression of adipocytokines. / Kang, Li; Sebastian, Becky M.; Pritchard, Michele T.; Pratt, Brian T.; Previs, Stephen F.; Nagy, Laura E.

In: Alcoholism: Clinical and Experimental Research, Vol. 31, No. 9, 11.07.2007, p. 1581-8.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Chronic ethanol-induced insulin resistance is associated with macrophage infiltration into adipose tissue and altered expression of adipocytokines

AU - Kang, Li

AU - Sebastian, Becky M.

AU - Pritchard, Michele T.

AU - Pratt, Brian T.

AU - Previs, Stephen F.

AU - Nagy, Laura E.

PY - 2007/7/11

Y1 - 2007/7/11

N2 - BACKGROUND: Chronic ethanol consumption disrupts glucose homeostasis and is associated with the development of insulin resistance. While adipose tissue and skeletal muscle are the two major organs utilizing glucose in response to insulin, the relative contribution of these two tissues to impaired glucose homeostasis during chronic ethanol feeding is not known. As other models of insulin resistance, such as obesity, are characterized by an infiltration of macrophages into adipose tissue, as well as changes in the expression of adipocytokines that play a central role in the regulation of insulin sensitivity, we hypothesized that chronic ethanol-induced insulin resistance would be associated with increased macrophage infiltration into adipose tissue and changes in the expression of adipocytokines by adipose tissue.METHODS: Male Wistar rats were fed a liquid diet containing ethanol as 36% of calories or pair-fed a control diet for 4 weeks. The effects of chronic ethanol feeding on insulin-stimulated glucose utilization were studied using the hyperinsulinemic-euglycemic clamp technique, coupled with the use of isotopic tracers. Further, macrophage infiltration into adipose tissue and expression of adipocytokines were also assessed after chronic ethanol feeding.RESULTS: Hyperinsulinemic-euglycemic clamp studies revealed that chronic ethanol feeding to rats decreased whole-body glucose utilization and decreased insulin-mediated suppression of hepatic glucose production. Chronic ethanol feeding decreased glucose uptake in epididymal, subcutaneous, and omental adipose tissue during the hyperinsulinemic-euglycemic clamp, but had no effect on glucose disposal in skeletal muscle. Chronic ethanol feeding increased the infiltration of macrophages into epididymal adipose tissue and changed the expression of mRNA for adipocytokines: expression of mRNA for monocyte chemoattractant protein 1, tumor necrosis factor alpha, and interleukin-6 were increased, while expression of mRNA for retinol binding protein 4 and adiponectin were decreased in epididymal adipose tissue.CONCLUSIONS: These data demonstrate that chronic ethanol feeding results in the development of insulin resistance, associated with impaired insulin-mediated suppression of hepatic glucose production and decreased insulin-stimulated glucose uptake into adipose tissue. Chronic ethanol-induced insulin resistance was associated with increased macrophage infiltration into adipose tissue, as well as changes in the expression of adipocytokines by adipose tissue.

AB - BACKGROUND: Chronic ethanol consumption disrupts glucose homeostasis and is associated with the development of insulin resistance. While adipose tissue and skeletal muscle are the two major organs utilizing glucose in response to insulin, the relative contribution of these two tissues to impaired glucose homeostasis during chronic ethanol feeding is not known. As other models of insulin resistance, such as obesity, are characterized by an infiltration of macrophages into adipose tissue, as well as changes in the expression of adipocytokines that play a central role in the regulation of insulin sensitivity, we hypothesized that chronic ethanol-induced insulin resistance would be associated with increased macrophage infiltration into adipose tissue and changes in the expression of adipocytokines by adipose tissue.METHODS: Male Wistar rats were fed a liquid diet containing ethanol as 36% of calories or pair-fed a control diet for 4 weeks. The effects of chronic ethanol feeding on insulin-stimulated glucose utilization were studied using the hyperinsulinemic-euglycemic clamp technique, coupled with the use of isotopic tracers. Further, macrophage infiltration into adipose tissue and expression of adipocytokines were also assessed after chronic ethanol feeding.RESULTS: Hyperinsulinemic-euglycemic clamp studies revealed that chronic ethanol feeding to rats decreased whole-body glucose utilization and decreased insulin-mediated suppression of hepatic glucose production. Chronic ethanol feeding decreased glucose uptake in epididymal, subcutaneous, and omental adipose tissue during the hyperinsulinemic-euglycemic clamp, but had no effect on glucose disposal in skeletal muscle. Chronic ethanol feeding increased the infiltration of macrophages into epididymal adipose tissue and changed the expression of mRNA for adipocytokines: expression of mRNA for monocyte chemoattractant protein 1, tumor necrosis factor alpha, and interleukin-6 were increased, while expression of mRNA for retinol binding protein 4 and adiponectin were decreased in epididymal adipose tissue.CONCLUSIONS: These data demonstrate that chronic ethanol feeding results in the development of insulin resistance, associated with impaired insulin-mediated suppression of hepatic glucose production and decreased insulin-stimulated glucose uptake into adipose tissue. Chronic ethanol-induced insulin resistance was associated with increased macrophage infiltration into adipose tissue, as well as changes in the expression of adipocytokines by adipose tissue.

KW - Adiponectin/metabolism

KW - Adipose Tissue/drug effects

KW - Alcoholism/metabolism

KW - Animals

KW - Cell Movement/drug effects

KW - Central Nervous System Depressants/adverse effects

KW - Chemokine CCL2/metabolism

KW - Cytokines/metabolism

KW - Disease Models, Animal

KW - Ethanol/adverse effects

KW - Glucose/metabolism

KW - Glucose Clamp Technique

KW - Insulin Resistance/physiology

KW - Interleukin-6/metabolism

KW - Macrophages/drug effects

KW - Male

KW - Muscle, Skeletal/metabolism

KW - Rats

KW - Rats, Wistar

KW - Retinol-Binding Proteins/metabolism

KW - Retinol-Binding Proteins, Plasma

KW - Tumor Necrosis Factor-alpha/metabolism

U2 - 10.1111/j.1530-0277.2007.00452.x

DO - 10.1111/j.1530-0277.2007.00452.x

M3 - Article

VL - 31

SP - 1581

EP - 1588

JO - Alcoholism: Clinical and Experimental Research

JF - Alcoholism: Clinical and Experimental Research

SN - 0145-6008

IS - 9

ER -