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

Abstract
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.
AuthorsRuth B S Harris
JournalAmerican journal of physiology. Endocrinology and metabolism (Am J Physiol Endocrinol Metab) Vol. 316 Issue 5 Pg. E719-E728 (05 01 2019) ISSN: 1522-1555 [Electronic] United States
PMID30721096 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Leptin
  • Receptors, Leptin
Topics
  • Adipose Tissue (drug effects)
  • Animals
  • Body Composition (drug effects)
  • Eating (drug effects)
  • Energy Metabolism
  • Fourth Ventricle (metabolism)
  • Hypothalamus (metabolism)
  • Injections, Intraventricular
  • Leptin (metabolism, pharmacology)
  • Male
  • Neural Pathways
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Leptin (metabolism)
  • Solitary Nucleus (metabolism)
  • Third Ventricle (metabolism)

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