Low dose infusions of leptin into the nucleus of the solitary tract increase sensitivity to third ventricle leptin.

Previous studies suggest that weight loss occurs when leptin receptors in both the forebrain and hindbrain are activated. Experiments described here tested whether this integration is mediated through a neural connection or by leptin diffusion through the subarachanoid space. If the hypothalamus and hindbrain communicated through a neural pathway, then a very low dose of leptin infused directly into the nucleus of the solitary tract (NTS) would enhance the response to third ventricle (3V) leptin, but would have no effect if infused into the fourth ventricle (4V). A 12 day infusion of 10 ng/24 hours into either the 4V or NTS reduced body fat. 5 ng leptin/24 hours into either the 4th ventricle or NTS had no effect on food intake or body composition, but infusion of 5 ng leptin/24 hours into the NTS combined with a 3V injection of 0.1 ug leptin inhibited food intake between 6 and 12 hours after injection. Cumulative intake was inhibited for up to 36 hours. 3V leptin had no effect on food intake of rats receiving 4V leptin infusion. Similar results were found using infusions of 5 ng leptin/24 hours and a 3V injection of 0.025 ug leptin. These data suggest that activation of leptin receptors in the NTS lowers the threshold for response to leptin in the forebrain through a neural network.