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Antagonistic modulation of NPY/AgRP and POMC neurons in the arcuate nucleus by noradrenalin

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Item Type:Article
Title:Antagonistic modulation of NPY/AgRP and POMC neurons in the arcuate nucleus by noradrenalin
Creators Name:Paeger, L. and Karakasilioti, I. and Altmüller, J. and Frommolt, P. and Brüning, J. and Kloppenburg, P.
Abstract:In the arcuate nucleus of the hypothalamus (ARH) satiety signaling (anorexigenic) pro-opiomelanocortin (POMC)-expressing and hunger signaling (orexigenic) agouti-related peptide (AgRP)-expressing neurons are key components of the neuronal circuits that control food intake and energy homeostasis. Here, we assessed whether the catecholamine noradrenalin directly modulates the activity of these neurons in mice. Perforated patch clamp recordings showed that noradrenalin changes the activity of these functionally antagonistic neurons in opposite ways, increasing the activity of the orexigenic NPY/AgRP neurons and decreasing the activity of the anorexigenic POMC neurons. Cell type-specific transcriptomics and pharmacological experiments revealed that the opposing effect on these neurons is mediated by the activation of excitatory α(1A) - and β- adrenergic receptors in NPY/AgRP neurons, while POMC neurons are inhibited via α(2A) - adrenergic receptors. Thus, the coordinated differential modulation of the key hypothalamic neurons in control of energy homeostasis assigns noradrenalin an important role to promote feeding.
Keywords:Agouti-Related Protein, Arcuate Nucleus of Hypothalamus, Gene Expression Profiling, Neurons, Norepinephrine, Patch-Clamp Techniques, Pro-Opiomelanocortin, Animals, Mice
Publisher:eLife Sciences Publications
Page Range:e25770
Date:20 June 2017
Official Publication:https://doi.org/10.7554/eLife.25770
PubMed:View item in PubMed

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