Adrenergic modulation of melanocortin pathway by hunger signals

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.

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Eser Adı
(dc.title)
Adrenergic modulation of melanocortin pathway by hunger signals
Yazar [Asıl]
(dc.creator.author)
Yılmaz, Bayram
Yazar [Asıl]
(dc.creator.author)
Yavuz, Yavuz
Yayın Tarihi
(dc.date.issued)
2023
Yazar Departmanı
(dc.creator.department)
Yeditepe University Faculty of Medicine
Yazar Departmanı
(dc.creator.department)
Yeditepe University Faculty of Medicine Department of Physiology
Yazar Orcid
(dc.creator.orcid)
0000-0002-2674-6535
Diğer Yazarlar
(dc.contributor.authors)
Sayar-Atasoy, Nilufer
Diğer Yazarlar
(dc.contributor.authors)
Laule, Connor
Diğer Yazarlar
(dc.contributor.authors)
Aklan, Iltan
Diğer Yazarlar
(dc.contributor.authors)
Kim, Hyojin
Diğer Yazarlar
(dc.contributor.authors)
Ates, Tayfun
Diğer Yazarlar
(dc.contributor.authors)
Coban, Ilknur
Diğer Yazarlar
(dc.contributor.authors)
Koksalar-Alkan, Fulya
Diğer Yazarlar
(dc.contributor.authors)
Rysted, Jacob
Diğer Yazarlar
(dc.contributor.authors)
Davis, Debbie
Diğer Yazarlar
(dc.contributor.authors)
Singh, Uday
Diğer Yazarlar
(dc.contributor.authors)
Alp, Muhammed Ikbal
Diğer Yazarlar
(dc.contributor.authors)
Cui, Huxing
Diğer Yazarlar
(dc.contributor.authors)
Atasoy, Deniz
Yazar [KatkıdaBulunan] Kurum
(dc.contributor.institution)
Yeditepe University Faculty of Medicine
Özet Bilgisi
(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.
Konu Başlıkları [Genel]
(dc.subject)
Brain
Konu Başlıkları [Genel]
(dc.subject)
Fasting
Konu Başlıkları [Genel]
(dc.subject)
Feeding Behavior
Konu Başlıkları [Genel]
(dc.subject)
Gene Expression
Konu Başlıkları [Genel]
(dc.subject)
Hunger
Konu Başlıkları [Genel]
(dc.subject)
Inhibition
Açık Erişim Tarihi
(dc.date.available)
2023-11-22
Açıklama [Genel]
(dc.description)
Final published version
Kayıt Giriş Tarihi
(dc.date.accessioned)
2023-11-22
Tanım Koleksiyon Bilgisi
(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
Açıklama [Not]
(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.
Yayın Türü [Ortam]
(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
Dil
(dc.language.iso)
eng
Yayıncı
(dc.publisher)
Springer Nature Limited
Haklar
(dc.rights)
Yeditepe University Academic and Open Access Information System
Erişim Hakkı
(dc.rights.access)
Open Access
Telif Hakkı
(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.
Telif Hakkı Url
(dc.rights.uri)
http://creativecommons.org/licenses/by-nc-nd/4.0
Telif Hakkı Url
(dc.rights.uri)
https://rightsstatements.org/page/InC-NC/1.0/?language=en
Yayın Turu [Akademik]
(dc.type)
Article
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