title: An Indirect Action Contributes to C-Fos Induction in Paraventricular Hypothalamic Nucleus by Neuropeptide Y.
abstract: Neuropeptide Y (NPY) is a well-established orexigenic peptide and hypothalamic paraventricular nucleus (PVH) is one major brain site that mediates the orexigenic action of NPY. NPY induces abundant expression of C-Fos, an indicator for neuronal activation, in the PVH, which has been used extensively to examine the underlying NPY orexigenic neural pathways. However, PVH C-Fos induction is in discordance with the abundant expression of NPY receptors, a group of inhibitory Gi protein coupled receptors in the PVH, and with the overall role of PVH neurons in feeding inhibition, suggesting a mechanism of indirect action. Here we showed that the ability of NPY on C-Fos induction in the PVH was blunted in conditions of insulin deficiency and fasting, a condition associated with a high level of NPY and a low level of insulin. Moreover, insulin insufficiency blunted C-Fos induction in the PVH by fasting-induced re-feeding, and insulin and NPY induced c-Fos induction in the same group of PVH neurons. Finally, NPY produced normal C-Fos induction in the PVH with disruption of GABA-A receptors. Thus, our results revealed that PVH C-Fos induction by NPY is mediated by an indirect action, which is at least partially mediated by insulin action, but not GABA-A receptors.
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.|Brown Foundation Institute of Molecular Medicine and Program in Neuroscience, Graduate School of Biological Sciences, University of Texas McGovern Medical School, Houston, TX 77030 USA.
authors.forename: Shengjie
authors.initials: S
authors.lastname: Fan
authors.affiliation: Brown Foundation Institute of Molecular Medicine and Program in Neuroscience, Graduate School of Biological Sciences, University of Texas McGovern Medical School, Houston, TX 77030 USA.
authors.forename: Janani
authors.initials: J
authors.lastname: Dakshinamoorthy
authors.affiliation: Brown Foundation Institute of Molecular Medicine and Program in Neuroscience, Graduate School of Biological Sciences, University of Texas McGovern Medical School, Houston, TX 77030 USA.
authors.forename: Eun Ran
authors.initials: ER
authors.lastname: Kim
authors.affiliation: Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.affiliation: Brown Foundation Institute of Molecular Medicine and Program in Neuroscience, Graduate School of Biological Sciences, University of Texas McGovern Medical School, Houston, TX 77030 USA.
authors.forename: Qingchun
authors.initials: Q
authors.lastname: Tong
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental; D003922:Diabetes Mellitus, Type 1; D005215:Fasting; D059330:GABAergic Neurons / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D007328:Insulin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009478:Neuropeptide Y / Q000378:metabolism* / Q000494:pharmacology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism
chemical_list: D007328:Insulin; D009478:Neuropeptide Y; D016760:Proto-Oncogene Proteins c-fos; D011963:Receptors, GABA-A
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