Effects of systemic inflammation on insulin sensitivity in horses and inflammatory cytokine expression in adipose tissue.
OBJECTIVE
To determine whether an inflammatory challenge induces insulin resistance in horses and examine possible contributions of adipose tissue to inflammatory cytokine production.


METHODS
15 adult mares.


METHODS
Lipopolysaccharide (0.045 mug/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
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.
Vick
Mandi M
MM
Gluck Equine Research Center, Department of Veterinary Science, College of Agriculture, University of Kentucky, Lexington, KY 40546, USA.
Murphy
Barbara A
BA
Sessions
Dawn R
DR
Reedy
Stephanie E
SE
Kennedy
Erin L
EL
Horohov
David W
DW
Cook
R Frank
RF
Fitzgerald
Barry P
BP
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006734:Horse Diseases / Q000139:chemically induced* / Q000378:metabolism; D006736:Horses; D007249:Inflammation / Q000139:chemically induced / Q000662:veterinary; D007333:Insulin Resistance / Q000502:physiology*; D013997:Time Factors
D016207:Cytokines