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 h into the 4V or the NTS reduced body fat.
Leptin at 5 ng/24 h into the 4V or NTS had no effect on food intake or body composition, but infusion of 5 ng of
leptin/24 h into the NTS combined with a 3V injection of 0.1 μg of
leptin inhibited food intake between 6 and 12 h after injection. Cumulative intake was inhibited for up to 36 h. 3V
leptin had no effect on food intake of rats receiving the 4V
leptin infusion. Similar results were found using infusions of 5 ng
leptin/24 h and a 3V injection of 0.025 μg
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.