Antagonistic modulation of NPY/AgRP and POMC neurons in the arcuate nucleus by noradrenalin
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. Her...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-06-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/25770 |
| _version_ | 1811199378466013184 |
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| author | Lars Paeger Ismene Karakasilioti Janine Altmüller Peter Frommolt Jens Brüning Peter Kloppenburg |
| author_facet | Lars Paeger Ismene Karakasilioti Janine Altmüller Peter Frommolt Jens Brüning Peter Kloppenburg |
| author_sort | Lars Paeger |
| collection | DOAJ |
| description | 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 α1A - and β- adrenergic receptors in NPY/AgRP neurons, while POMC neurons are inhibited via α2A – 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. |
| first_indexed | 2024-04-12T01:47:19Z |
| format | Article |
| id | doaj.art-6232edad4886450f92fb8fb198c1e1ec |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:47:19Z |
| publishDate | 2017-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-6232edad4886450f92fb8fb198c1e1ec2022-12-22T03:53:02ZengeLife Sciences Publications LtdeLife2050-084X2017-06-01610.7554/eLife.25770Antagonistic modulation of NPY/AgRP and POMC neurons in the arcuate nucleus by noradrenalinLars Paeger0https://orcid.org/0000-0001-8716-3483Ismene Karakasilioti1Janine Altmüller2Peter Frommolt3Jens Brüning4Peter Kloppenburg5https://orcid.org/0000-0002-4554-404XBiocenter, Institute for Zoology, University of Cologne, Cologne, Germany; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, Cologne, GermanyExcellence Cluster on Cellular Stress Responses in Aging Associated Diseases, Cologne, Germany; Max Planck Institute for Metabolism Research, Cologne, Germany; Center of Molecular Medicine Cologne, University of Cologne, Cologne, Germany; Center for Endocrinology, Diabetes and Preventive Medicine, University Hospital Cologne, Cologne, GermanyCenter of Molecular Medicine Cologne, University of Cologne, Cologne, Germany; Cologne Center for Genomics, University of Cologne, Cologne, GermanyBioinformatics Facility, Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, Cologne, GermanyExcellence Cluster on Cellular Stress Responses in Aging Associated Diseases, Cologne, Germany; Max Planck Institute for Metabolism Research, Cologne, Germany; Center of Molecular Medicine Cologne, University of Cologne, Cologne, Germany; Center for Endocrinology, Diabetes and Preventive Medicine, University Hospital Cologne, Cologne, GermanyBiocenter, Institute for Zoology, University of Cologne, Cologne, Germany; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, Cologne, GermanyIn 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 α1A - and β- adrenergic receptors in NPY/AgRP neurons, while POMC neurons are inhibited via α2A – 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.https://elifesciences.org/articles/25770noradrenalinneuromodulationAgRP-neuronPOMC-neuron |
| spellingShingle | Lars Paeger Ismene Karakasilioti Janine Altmüller Peter Frommolt Jens Brüning Peter Kloppenburg Antagonistic modulation of NPY/AgRP and POMC neurons in the arcuate nucleus by noradrenalin eLife noradrenalin neuromodulation AgRP-neuron POMC-neuron |
| title | Antagonistic modulation of NPY/AgRP and POMC neurons in the arcuate nucleus by noradrenalin |
| title_full | Antagonistic modulation of NPY/AgRP and POMC neurons in the arcuate nucleus by noradrenalin |
| title_fullStr | Antagonistic modulation of NPY/AgRP and POMC neurons in the arcuate nucleus by noradrenalin |
| title_full_unstemmed | Antagonistic modulation of NPY/AgRP and POMC neurons in the arcuate nucleus by noradrenalin |
| title_short | Antagonistic modulation of NPY/AgRP and POMC neurons in the arcuate nucleus by noradrenalin |
| title_sort | antagonistic modulation of npy agrp and pomc neurons in the arcuate nucleus by noradrenalin |
| topic | noradrenalin neuromodulation AgRP-neuron POMC-neuron |
| url | https://elifesciences.org/articles/25770 |
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