Improvement in insulin resistance and reduction in plasma inflammatory adipokines after weight loss in obese dogs

Obesity is now a major disease of dogs, predisposing to numerous disorders including diabetes mellitus. Adipocytes are active endocrine cells, and human obesity is characterized by derangements in inflammatory adipokine production. However, it is unclear as to whether similar changes occur in dogs. The purpose of the current study was to assess insulin sensitivity and inflammatory adipokine profiles in dogs with naturally occurring obesity and to investigate the effect of subsequent weight loss. Twenty-six overweight dogs were studied, representing a range of breeds and both sexes. All dogs underwent a weight loss program involving diet and exercise. Body fat mass was measured by dual-energy x-ray absorptiometry; plasma concentrations of insulin, glucose, and a panel of inflammatory adipokines (including acute-phase proteins, cytokines, and chemokines) were also analyzed. Body fat mass before weight loss was positively correlated with both plasma insulin concentrations (Kendall τ=0.30, P=0.044) and insulin:glucose ratio (Kendall τ=0.36, P=0.022), and both decreased after weight loss (P=0.0037 and 0.0063, respectively). Weight loss also led to notable decreases in plasma tumor necrosis factor-α (TNF-α), haptoglobin, and C-reactive protein concentrations (P<0.05 for all), suggesting improvement of a subclinical inflammatory state associated with obesity. This study has demonstrated that in obese dogs, insulin resistance correlates with degree of adiposity, and weight loss improves insulin sensitivity. Concurrent decreases in TNF-α and adipose tissue mass suggest that in dogs, as in humans, this adipokine may be implicated in the insulin resistance of obesity.