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A Potential Role for Pro-Inflammatory Cytokines in the Development of Insulin Resistance in Horses
Department of Dairy Science, Virginia Tech, Blacksburg, VA 24071, USA
Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, MI 48824, USA
* Author to whom correspondence should be addressed.
Received: 1 March 2012; in revised form: 16 April 2012 / Accepted: 26 April 2012 / Published: 2 May 2012
Simple Summary: Insulin resistance is a metabolic condition involving reduced sensitivity of insulin-sensitive tissues to insulin-induced glucose disposal, including adipose tissue, skeletal muscle, and liver. Insulin resistance occurs in overweight and obese horses, and may increase risk for the development of laminitis. The development of insulin resistance is thought to occur in response to increased production of pro-inflammatory cytokines by adipose tissue in obesity, that then have an inhibitory effect on insulin signaling pathways in multiple tissues. This article reviews current knowledge of the involvement of pro-inflammatory cytokines in the development of insulin resistance in horses and uses data from other species to provide context.
Abstract: Understanding the mechanisms involved in the development of insulin resistance in horses should enable development of effective treatment and prevention strategies. Current knowledge of these mechanisms is based upon research in obese humans and rodents, in which there is evidence that the increased production of pro-inflammatory cytokines by adipose tissue negatively influences insulin signaling in insulin-responsive tissues. In horses, plasma concentrations of the cytokine, tumor necrosis factor-α, have been positively correlated with body fatness and insulin resistance, leading to the hypothesis that inflammation may reduce insulin sensitivity in horses. However, little evidence has documented a tissue site of production and a direct link between inflammation and induction of insulin resistance has not been established. Several mechanisms are reviewed in this article, including the potential for macrophage infiltration, hyperinsulinemia, hypoxia, and lipopolysaccharide to increase pro-inflammatory cytokine production by adipose tissue of obese horses. Clearly defining the role of cytokines in reduced insulin sensitivity of horses will be a very important step in determining how obesity and insulin resistance are related.
Keywords: adipose tissue; horses; inflammation; obesity; pro-inflammatory cytokines; skeletal muscle
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Suagee, J.K.; Corl, B.A.; Geor, R.J. A Potential Role for Pro-Inflammatory Cytokines in the Development of Insulin Resistance in Horses. Animals 2012, 2, 243-260.
Suagee JK, Corl BA, Geor RJ. A Potential Role for Pro-Inflammatory Cytokines in the Development of Insulin Resistance in Horses. Animals. 2012; 2(2):243-260.
Suagee, Jessica K.; Corl, Benjamin A.; Geor, Raymond J. 2012. "A Potential Role for Pro-Inflammatory Cytokines in the Development of Insulin Resistance in Horses." Animals 2, no. 2: 243-260.