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Histochemical approaches to understanding central regulation of food intake by melanocortin signaling
Author(s) -
Blevins James Ernest,
Morton Gregory James,
Williams Diana Leigh,
Schwartz Michael Warren
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.108
Subject(s) - melanocortin , melanocortin 3 receptor , hypothalamus , melanocortin 4 receptor , medicine , endocrinology , cholecystokinin , melanocortin receptor , receptor , agonist , biology , cholera toxin , oxytocin
It has been established that activation of melanocortin receptors (MC3/MC4R) in the hypothalamus results in a reduction of food intake, but the mechanism is unknown. Using the MC3/MC4R agonist, MTII, and histochemical techniques, we tested the hypothesis that melanocortin signaling increases CNS sensitivity to satiety signals. We found that CNS injection of MTII enhanced the ability of the satiety signal cholecystokinin (CCK) to reduce feeding and induce c‐Fos in the NTS. To locate hypothalamic neurons transmitting this signaling to the NTS, parvocellular PVN (pPVN) cells projecting to the NTS were identified by injection of the retrograde tracer, fluorescent cholera toxin B (fCTB) in the NTS. Cells in the pPVN that showed fCTB signal showed oxytocin (OXY) immunoreactivity. We used laser capture microdissection to collect pPVN cells containing the fCTB and pooled these cells for real‐time quantitative PCR analysis of MC4R mRNA. pPVN neurons that project to the NTS expressed MC4R mRNA in addition to OXY and CRH mRNA, thus confirming a neuroanatomical pathway from the pPVN to the NTS for the anorexic effects of melanocortin ligands in the hypothalamus. These findings support a model in which OXY and CRH neurons in the PVN respond to melanocortin receptor activation by acting on NTS neurons to enhance the behavioral response to CCK. Support: NIH DK‐17047, DK‐52989, DK‐12829, NIDDK, 5P30 DK35816‐18, NS‐32273, VA MR.