Body weight reduction in rats by oral treatment with zinc plus cyclo-(His-Pro).

Background and purpose: We have previously shown that treatment with zinc plus cyclo-(His-Pro) (CHP) significantly stimulated synthesis of the insulin degrading enzyme and lowered plasma insulin and blood glucose levels, alongside improving oral glucose tolerance in genetically type 2 diabetic Goto-Kakizaki (G-K) rats and in aged obese Sprague-Dawley (S-D) rats. Thus, we postulated that zinc plus CHP (ZC) treatment might also improve body weight control in these rats. We therefore determined the effects of ZC treatment on body weights in both genetically diabetic, mature G-K rats and non-diabetic, obese S-D rats. Experimental approach: G-K rats aged 1.5-10 months and non-diabetic overweight or obese S-D rats aged 6-18 months were treated with 0-6 mg CHP plus 0-10 mg zinc center dot L-1 drinking water for 2-4 weeks, and changes in weight, serum leptin and adiponectin levels, food and water intakes were measured. Key results: The optimal dose of CHP (in combination with zinc) to reduce weight and plasma leptin levels and to increase plasma adiponectin levels was close to 0.1 mg center dot kg(-1)center dot day(-1), in either mature G-K rats and aged overweight or obese S-D rats. Food and water intake significantly decreased in ZC treated rats in both aged S-D rats and mature G-K rats, but not in young S-D and G-K rats. Conclusions and implications: ZC treatment improved weight control and may be a possible treatment for overweight and obesity.