Transient effects of long-term leptin supplementation in the prevention ofdiet-induced obesity in mice

Low plasma leptin levels have been shown to be associated with the developm ent of obesity in mice as well as in humans. The present study was undertak en to determine if raising plasma leptin levels of obesity-prone C57BL/6J ( B6) mice to those seen in obesity-resistant A/J mice would prevent the deve lopment of diet-induced obesity. Four-week-old B6 (n = 40) and A/J (n = 10) male mice were weaned onto a low-fat (11% kcal) diet. When the animals wei ghed 20 g, their diets were changed to a high-fat (HF) diet (58% kcal), and a continuous infusion of leptin (0.4 mg . kg(-1) . day(-1)) or phosphate-b uffered saline (control) was started using Alzet minipumps. The A/J mice we re not treated but were included to monitor the efficacy of the minipumps i n raising plasma leptin in B6 mice. The mice were followed for 12 weeks. Ch ronic treatment with leptin for 4 weeks raised plasma levels in B6 mice to that of A/J mice. Plasma leptin in B6 control mice remained significantly l ower than A/J mice through week 4. By week 8, leptin levels in the B6 contr ol group had risen and were similar to A/J mice. Although there were signif icant weight differences between B6 treated and B6 control groups for 2-3 w eeks after pump implantation, these differences were transient. Ultimately, there were no weight differences between the B6 treated and B6 control gro ups. There were no differences in plasma glucose between B6 treated and con trol groups. Plasma insulin values were also not different between the 2 gr oups. There was no effect of leptin supplementation on locomotor activity o r food intake in B6 mice. In summary, this study demonstrates that leptin s upplementation in animals that show low plasma leptin levels in response to fat feeding may slow but does not prevent the subsequent development of di et-induced obesity.