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Effects of systemic inflammation on insulin sensitivity in horses and inflammatory cytokine expression in adipose tissue

Mandi M. VickGluck Equine Research Center, Department of Veterinary Science, College of Agriculture, University of Kentucky, Lexington, KY 40546.

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Barbara A. MurphyGluck Equine Research Center, Department of Veterinary Science, College of Agriculture, University of Kentucky, Lexington, KY 40546.

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Dawn R. SessionsGluck Equine Research Center, Department of Veterinary Science, College of Agriculture, University of Kentucky, Lexington, KY 40546.

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Stephanie E. ReedyGluck Equine Research Center, Department of Veterinary Science, College of Agriculture, University of Kentucky, Lexington, KY 40546.

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Erin L. KennedyGluck Equine Research Center, Department of Veterinary Science, College of Agriculture, University of Kentucky, Lexington, KY 40546.

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David W. HorohovGluck Equine Research Center, Department of Veterinary Science, College of Agriculture, University of Kentucky, Lexington, KY 40546.

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R. Frank CookGluck Equine Research Center, Department of Veterinary Science, College of Agriculture, University of Kentucky, Lexington, KY 40546.

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Barry P. FitzgeraldGluck Equine Research Center, Department of Veterinary Science, College of Agriculture, University of Kentucky, Lexington, KY 40546.

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Abstract

Objective—To determine whether an inflammatory challenge induces insulin resistance in horses and examine possible contributions of adipose tissue to inflammatory cytokine production.

Animals—15 adult mares.

Procedures—Lipopolysaccharide (0.045 μg/kg, IV) or saline solution was administered, and insulin sensitivity was determined by means of the hyperinsulinemic, euglycemic clamp procedure or an adipose tissue biopsy was performed. Adipose tissue samples were collected, and mature adipocytes were obtained. Mature adipocytes were stimulated with lipopolysaccharide or dedifferentiated into preadipocytes and then stimulated with lipopolysaccharide. Interleukin-1, interleukin-6, and tumor necrosis factor A expression in blood, adipose tissue, and adipocytes was quantified with a real-time, reverse transcriptase– PCR assay.

Results—Lipopolysaccharide induced a transient increase in insulin sensitivity followed by a reduction in insulin sensitivity at 24 hours. Increased cytokine expression was observed in blood and adipose tissue following administration of lipopolysaccharide, and adipocytes and preadipocytes stimulated with lipopolysaccharide stained positive for tumor necrosis factor A. Expression of interleukin-1, interleukin-6, and tumor necrosis factor A was detected in preadipocytes stimulated with lipopolysaccharide, and interleukin-6 and tumor necrosis factor A were detected in mature adipocytes stimulated with lipopolysaccharide.

Conclusions and Clinical Relevance—Results indicated that insulin resistance develops following systemic inflammation in horses and suggested that adipose tissue may contribute to this inflammatory response. Methods to regulate insulin sensitivity may improve clinical outcome in critically ill patients.

Abstract

Objective—To determine whether an inflammatory challenge induces insulin resistance in horses and examine possible contributions of adipose tissue to inflammatory cytokine production.

Animals—15 adult mares.

Procedures—Lipopolysaccharide (0.045 μg/kg, IV) or saline solution was administered, and insulin sensitivity was determined by means of the hyperinsulinemic, euglycemic clamp procedure or an adipose tissue biopsy was performed. Adipose tissue samples were collected, and mature adipocytes were obtained. Mature adipocytes were stimulated with lipopolysaccharide or dedifferentiated into preadipocytes and then stimulated with lipopolysaccharide. Interleukin-1, interleukin-6, and tumor necrosis factor A expression in blood, adipose tissue, and adipocytes was quantified with a real-time, reverse transcriptase– PCR assay.

Results—Lipopolysaccharide induced a transient increase in insulin sensitivity followed by a reduction in insulin sensitivity at 24 hours. Increased cytokine expression was observed in blood and adipose tissue following administration of lipopolysaccharide, and adipocytes and preadipocytes stimulated with lipopolysaccharide stained positive for tumor necrosis factor A. Expression of interleukin-1, interleukin-6, and tumor necrosis factor A was detected in preadipocytes stimulated with lipopolysaccharide, and interleukin-6 and tumor necrosis factor A were detected in mature adipocytes stimulated with lipopolysaccharide.

Conclusions and Clinical Relevance—Results indicated that insulin resistance develops following systemic inflammation in horses and suggested that adipose tissue may contribute to this inflammatory response. Methods to regulate insulin sensitivity may improve clinical outcome in critically ill patients.

Contributor Notes

Dr. Vick's present address is Smithsonian Institute's National Zoo, Center for Research and Conservation, Department of Reproductive Sciences, 1500 Remount Rd, Front Royal, VA 22630.

Supported by the Kentucky Equine Research Foundation.

Presented in part at the Waltham International Nutritional Sciences Symposium on Equine Laminitis, Washington, DC, September 2005.

The research reported in this article (No. 07-14-079) is published in connection with a project of the Kentucky Agricultural Experiment Station and is published with approval of its director.

The authors thank Rhonda Van Dyke for assistance with statistical analyses.

Address correspondence to Dr. Fitzgerald.