Leptin-derived peptides that stimulate food intake and increase body weight following peripheral administration

We previously showed that peptides containing leptin sequences 1–33 or 61–90 are taken up by the rat brain. We now report the effects of these peptides on food intake and body weight in mature rats. Peptides were infused intravenously for 4 weeks, using Alzet minipumps. Dosages were 20 μg/kg/day in experiment I, and 60 μg/kg/day in experiment 2. In experiment 1, female rats receiving peptides 1–33 and 61–90 each underwent an approximate doubling of the weight gain of control rats. These peptides also increased food intake in female rats. Peptide 15–32, which has a lesser degree of brain uptake, gave a smaller weight gain. Peptide 83–108, which is not taken up by the brain, had no effect on weight gain or food intake. Similar results were obtained in experiment 2. In male rats, however, none of the peptides caused significant changes in food intake or body weight. This was at least partly due to the fact that all male rats underwent vigorous weight increases. We conclude that peptides 1–33 and 61–90 acted as leptin antagonists, stimulating food intake and body weight increases, at least in female rats. These peptides may lead to clinical applications in conditions such as anorexia and cachexia.