Norepinephrine (NE) is a well-known appetite regulator, and the nor/adrenergic system is targeted by several anti-obesity drugs. To better understand the circuitry underlying adrenergic appetite control, here we investigated the paraventricular hypothalamic nucleus (PVN), a key brain region that integrates energy signals and receives dense nor/adrenergic input, using a mouse model. We found that PVN NE level increases with signals of energy deficit and decreases with food access. This pattern is recapitulated by the innervating catecholaminergic axon terminals originating from NTSTH-neurons. Optogenetic activation of rostral-NTSTH → PVN projection elicited strong motivation to eat comparable to overnight fasting whereas its inhibition attenuated both fasting-induced & hypoglycemic feeding. We found that NTSTH-axons functionally targeted PVNMC4R-neurons by predominantly inhibiting them, in part, through α1-AR mediated potentiation of GABA release from ARCAgRP presynaptic terminals. Furthermore, glucoprivation suppressed PVNMC4R activity, which was required for hypoglycemic feeding response. These results define an ascending nor/adrenergic circuit, NTSTH → PVNMC4R, that conveys peripheral hunger signals to melanocortin pathway. © 2023, Springer Nature Limited.
اسم العمل (dc.title) | Adrenergic modulation of melanocortin pathway by hunger signals |
(dc.creator.author) | Yılmaz, Bayram |
(dc.creator.author) | Yavuz, Yavuz |
تاريخ النشر (dc.date.issued) | 2023 |
(dc.creator.department) | Yeditepe University Faculty of Medicine |
(dc.creator.department) | Yeditepe University Faculty of Medicine Department of Physiology |
(dc.creator.orcid) | 0000-0002-2674-6535 |
(dc.contributor.authors) | Sayar-Atasoy, Nilufer |
(dc.contributor.authors) | Laule, Connor |
(dc.contributor.authors) | Aklan, Iltan |
(dc.contributor.authors) | Kim, Hyojin |
(dc.contributor.authors) | Ates, Tayfun |
(dc.contributor.authors) | Coban, Ilknur |
(dc.contributor.authors) | Koksalar-Alkan, Fulya |
(dc.contributor.authors) | Rysted, Jacob |
(dc.contributor.authors) | Davis, Debbie |
(dc.contributor.authors) | Singh, Uday |
(dc.contributor.authors) | Alp, Muhammed Ikbal |
(dc.contributor.authors) | Cui, Huxing |
(dc.contributor.authors) | Atasoy, Deniz |
(dc.contributor.institution) | Yeditepe University Faculty of Medicine |
(dc.description.abstract) | Norepinephrine (NE) is a well-known appetite regulator, and the nor/adrenergic system is targeted by several anti-obesity drugs. To better understand the circuitry underlying adrenergic appetite control, here we investigated the paraventricular hypothalamic nucleus (PVN), a key brain region that integrates energy signals and receives dense nor/adrenergic input, using a mouse model. We found that PVN NE level increases with signals of energy deficit and decreases with food access. This pattern is recapitulated by the innervating catecholaminergic axon terminals originating from NTSTH-neurons. Optogenetic activation of rostral-NTSTH → PVN projection elicited strong motivation to eat comparable to overnight fasting whereas its inhibition attenuated both fasting-induced & hypoglycemic feeding. We found that NTSTH-axons functionally targeted PVNMC4R-neurons by predominantly inhibiting them, in part, through α1-AR mediated potentiation of GABA release from ARCAgRP presynaptic terminals. Furthermore, glucoprivation suppressed PVNMC4R activity, which was required for hypoglycemic feeding response. These results define an ascending nor/adrenergic circuit, NTSTH → PVNMC4R, that conveys peripheral hunger signals to melanocortin pathway. © 2023, Springer Nature Limited. |
(dc.subject) | Brain |
(dc.subject) | Fasting |
(dc.subject) | Feeding Behavior |
(dc.subject) | Gene Expression |
(dc.subject) | Hunger |
(dc.subject) | Inhibition |
Açık Erişim Tarihi (dc.date.available) | 2023-11-22 |
(dc.description) | Final published version |
Kayıt Giriş Tarihi (dc.date.accessioned) | 2023-11-22 |
(dc.description.collectioninformation) | This item is part of the preprint collection made available through Yeditepe University library. For your questions, our contact address is openaccess@yeditepe.edu.tr |
(dc.description.note) | Note: This preprint reports new research that has not been certified by peer review and should not be used as established information without consulting multiple experts in the field. |
(dc.format) | application/pdf |
DOI Numarası (dc.identifier.doi) | 10.1038/s41467-023-42362-8 |
Tek Biçim Adres (dc.identifier.uri) | https://hdl.handle.net/20.500.11831/8139 |
اللغة (dc.language.iso) | eng |
Yayıncı (dc.publisher) | Springer Nature Limited |
Haklar (dc.rights) | Yeditepe University Academic and Open Access Information System |
(dc.rights.access) | Open Access |
(dc.rights.holder) | Unless otherwise stated, copyrights belong to Yeditepe University. Usage permissions are specified in the Open Access System, and "InC-NC/1.0" and "by-nc-nd/4.0" are as stated. |
(dc.rights.uri) | http://creativecommons.org/licenses/by-nc-nd/4.0 |
(dc.rights.uri) | https://rightsstatements.org/page/InC-NC/1.0/?language=en |
(dc.type) | Article |