NDLI: Leptin differentially regulates NPY secretion in hypothalamic cell lines through distinct intracellular signal transduction pathways.

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Leptin differentially regulates NPY secretion in hypothalamic cell lines through distinct intracellular signal transduction pathways.

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Leptin differentially regulates NPY secretion in hypothalamic cell lines through distinct intracellular signal transduction pathways.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Dhillon, Sandeep S. Belsham, Denise D.
Description	Country affiliation: Canada Author Affiliation: Dhillon SS ( Departments of Physiology, Obstetrics and Gynaecology and Medicine, University of Toronto, ON, Canada.)
Abstract	Leptin acts as a key peripheral hormone in distinct neurons in the hypothalamus to modulate both reproductive function and energy homeostasis. The control of neuropeptide Y (NPY) secretion is an example of a process that can be differentially regulated by leptin. In order to further understand these distinct modulatory effects, we have used immortalized, neuronal hypothalamic cell lines expressing NPY, mHypoE-38 and mHypoE-46. We found that these cell lines express the endogenous leptin receptor, ObRb, and secrete detectable levels of NPY. We exposed the neurons to 100nM leptin for 1h and determined that the basal levels of NPY in the cell lines were differentially regulated: NPY secretion was inhibited in mHypoE-46 neurons, whereas NPY secretion was induced in the mHypoE-38 neurons. In order to determine the mechanisms involved in the divergent regulation of NPY release, we analyzed the activity of a number of signaling components using phospho-specific antibodies directed towards specific proteins in the MAP kinase, PI3K, and AMPK pathways, among others. We found that leptin activated a different combination of second messengers in each cell line. Importantly, we could link the regulation of NPY secretion to different signaling pathways, AMPK in the mHypoE-46 and both MAPK and PI3K in the mHypoE-38 neurons. This is the first demonstration that leptin can specifically regulate individual NPY neuron secretory responses through distinct signaling pathways.
File Format	HTM / HTML
ISSN	01670115
Issue Number	2-3
Volume Number	167
e-ISSN	18731686
Journal	Regulatory Peptides
Language	English
Publisher	Elsevier
Publisher Date	2011-04-11
Publisher Place	Netherlands
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Biochemistry Hypothalamus Metabolism Leptin Pharmacology Neuropeptide Y Secretion Signal Transduction Animals Cell Line Drug Effects Map Kinase Signaling System Physiology Neurons Phosphatidylinositol 3-kinases Protein Kinases Rats Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Physiology Clinical Biochemistry Biochemistry Cellular and Molecular Neuroscience Endocrinology

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