@article{d20914d36ed341e89c33154f6e0cac06,
title = "Leptin modulation of peripheral controls of meal size",
abstract = "Leptin reduces food intake through a specific effect on meal size. Investigations into how this within meal effect of leptin is mediated have demonstrated that leptin increases the ability of within meal inhibitory feedback signaling to limit intake and activate neurons within the nucleus of the solitary tract (NTS). Leptin's effects on neural activation can be demonstrated both as an increase in c-fos activation and as increase in electrophysiolgoical activity in response to peripheral stimuli. Leptin can exert these effects through interactions at hypothalamic sites and activation of a descending pathway. NPY has opposite effect suggesting a role for reduced NPY signaling in the actions of leptin. Forebrain ventricular administration of a melanocortin agonist does not mimic the actions of leptin. As well as modulating within meal signaling through a descending pathway leptin, NPY and melanocortins could work directly at hindbrain integrative sites suggesting the possibility of distributed controls of meal size by anorexigenic and orexigenic signaling.",
keywords = "Leptin, Melanocortin, NPY, Nucleus of the solitary tract, Satiety",
author = "Moran, {Timothy H.} and Susan Aja and Ladenheim, {Ellen E.}",
note = "Funding Information: The next questions were how and where this action of leptin was mediated. There are multiple possibilities. We had suggested that the effects of leptin on CCK satiety were mediated through hypothalamic sites and the excitation of descending pathways that then modified the responsivity of NTS neurons [32] . A hypothalamic site of action for leptin in modulating meal size is supported by recent work from Morton and colleagues [33] . They took advantage of the genetic defect in Koletsky rats that lack the leptin receptor and develop hyperphagia and severe obesity. They demonstrated that such rats had increased meal size and reduced response to exogenous CCK administration. Using an adenovirus expressing leptin receptors, they restored leptin signaling specifically to the hypothalamic arcuate nucleus. Restoration of arcuate leptin signaling reduced meal size and normalized the satiety response to exogenous CCK. Consistent with prior work demonstrating leptin/CCK interactions in NTS activation, rats with restored arcuate leptin signaling also had normalized NTS c-fos activation in response to CCK administration. These data demonstrate that leptin activation of the hypothalamic arcuate nucleus is sufficient for leptin mediated effects on meals size and modulation of within meal satiety signaling. ",
year = "2006",
month = nov,
day = "30",
doi = "10.1016/j.physbeh.2006.04.020",
language = "English (US)",
volume = "89",
pages = "511--516",
journal = "Physiology and Behavior",
issn = "0031-9384",
publisher = "Elsevier Inc.",
number = "4",
}