Increased Adiposity in Horses is Associated with Decreased Insulin Sensitivity but Unchanged Inflammatory Cytokine Expression in Subcutaneous Adipose Tissue
Obesity and insulin resistance (IR) in horses are of intense interest to the equine practitioner due to associated sequelae, including laminitis. In humans and in animal models of obesity, increased adiposity leads to a chronic inflammatory state which underlies the IR. This study investigated whether an increase in adiposity over time in horses is also associated with changes in insulin sensitivity and expression of inflammatory (circulating and subcutaneous adipose tissue) cytokines. To induce weight gain, 12 Arabian geldings were fed 200% of their digestible energy requirements for 4 months. Before and after weight gain, adiposity was measured, subcutaneous adipose tissue biopsies were obtained from the nuchal crest, and frequently sampled intravenous glucose tolerance tests were performed and assessed by the minimal model of glucose and insulin dynamics. Real time quantitative PCR was performed on the adipose tissue biopsy samples to assess mRNA concentrations of inflammatory genes (TNF-α, IL-1β, IL-6, IL-8, IL-10), and plasma concentrations of TNF-α were measured by ELISA (Endogen Inc.). Data were analyzed by the Mann-Whitney U test (α = 0.05) and are reported as median (interquartile range). At the end of the trial, body weight was increased (P = 0.001) by 18%, percent body fat estimated from subcutaneous fat thickness (ultrasonic assessment) had increased (P = 0.002) from 14 (12-18)% to 23 (19-26)%, and resting insulin concentration was increased (P < 0.001) from 4.3 (3.5-6.3) to 28 (20-43) mU/L. Insulin sensitivity decreased (P < 0.001) to 1/4 its original value, accompanied by an over fourfold increase (P < 0.001) in acute insulin response to glucose. These changes resulted in a similar disposition index (P = 1.0), indicating that decreased insulin sensitivity was effectively compensated for by an increased insulin secretory response. In contrast to the majority of data in human obesity, the decrease in insulin sensitivity was not associated with increases in indicators of inflammation. Plasma concentrations of TNF-α and adipose tissue mRNA expression of TNF-α, IL-1β, IL-6, IL-8, and IL-10 did not differ (P > 0.05) between pre- and post-weight gain samples. Thus, the results of this study demonstrate that in horses an acute increase in adiposity is associated with decreased insulin sensitivity and a compensatory increase in insulin secretory response independent of changes in the currently measured inflammatory cytokine expression in a subcutaneous fat depot.