Pioglitazone increases adiponectin and attenuates the appearance of diet-induced insulin resistance in high-fat-fed beagles

This study investigated the efficacy of thiazolidinediones in mitigating diet-induced obesity and associated glucose intolerance in canines in vivo. We used a multi technique approach and compared the results related to a) fasting metabolites, hormones, and lipides, b) oral glucose tolerance (OGTT), and c) hyperinsulinemic euglycemic (HIEG) clamps in 24 healthy dogs that were then fed a high fat diet and assigned to a placebo group (n=8) or received a daily dose of pioglitazone group (n=16) for 56 days. The animals are their own controls and we used a principal component analysis to combine the results obtained for the 3 different techniques. Both groups experienced weight gain, with 12% and 14% increases in the placebo and pioglitazone groups, respectively. The fasting level of free fatty acids were increased in both placebo (+17.5%) and pioglitazone groups (+7.7%), as were the insulin levels (+27 and 35% respectively in placebo and pioglitazone) but fasting glucose levels were reduced slightly in both (-2.7 and -2.9mg/dL respectively). Pioglitazone increased fasting adiponectin levels by 54% between Day-1 and Day 56. OGTTs revealed a significantly betterglucose tolerance in the pioglitazone treatment group compared to the placebo group as the level of insulin secreted during the OGTT was normalized. HIEG clamps demonstrated that, in the placebo group, glucose infusion rate and glucose utilization decreased in response to the diet but this effect was prevented by pioglitazone. In conclusion, these findings show that pioglitazone is beneficial in preventing the consequences of dietary metabolic stress and overfeeding in canines.