Adrenergic modulation of melanocortin pathway by hunger signals

Nilufer Sayar-Atasoy; Connor Laule; Iltan Aklan; Hyojin Kim; Yavuz Yavuz; Tayfun Ates; Ilknur Coban; Fulya Koksalar-Alkan; Jacob Rysted; Debbie Davis; Uday Singh; Muhammed Ikbal Alp; Bayram Yilmaz; Huxing Cui; Deniz Atasoy

doi:10.1038/s41467-023-42362-8

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Adrenergic modulation of melanocortin pathway by hunger signals

Journal article

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Adrenergic modulation of melanocortin pathway by hunger signals

Nilufer Sayar-Atasoy, Connor Laule, Iltan Aklan, Hyojin Kim, Yavuz Yavuz, Tayfun Ates, Ilknur Coban, Fulya Koksalar-Alkan, Jacob Rysted, Debbie Davis, …

Nature communications, Vol.14(1), 6602

01/01/2023

DOI: 10.1038/s41467-023-42362-8

PMCID: PMC10587058

PMID: 37857606

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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. Melanocortin pathway’s role in appetite regulation is a well-stablished. Here, authors describe a novel mechanism by which melanocortin pathway is regulated by ascending adrenergic input from brainstem during hunger and hypoglycemia.

Neurons

Appetite

Axon guidance

Axons

Brain stem

Circuits

Fasting

Feeding

Hunger

Hypoglycemia

Hypothalamus

Melanocortin

Mouse devices

Norepinephrine

Potentiation

Presynapse

γ-Aminobutyric acid

Details

Title: Subtitle: Adrenergic modulation of melanocortin pathway by hunger signals
Creators: Nilufer Sayar-Atasoy
Connor Laule - University of Iowa
Iltan Aklan - University of Iowa
Hyojin Kim - University of Iowa
Yavuz Yavuz - Yeditepe University
Tayfun Ates - University of Iowa
Ilknur Coban - Heidelberg University
Fulya Koksalar-Alkan - Wayne State University
Jacob Rysted - University of Iowa
Debbie Davis - University of Iowa
Uday Singh - University of Iowa
Muhammed Ikbal Alp
Bayram Yilmaz
Huxing Cui - University of Iowa
Deniz Atasoy - University of Iowa
Resource Type: Journal article
Publication Details: Nature communications, Vol.14(1), 6602
DOI: 10.1038/s41467-023-42362-8
PMID: 37857606
PMCID: PMC10587058
NLM abbreviation: Nat Commun
eISSN: 2041-1723
Publisher: Nature Publishing Group
Language: English
Date published: 01/01/2023
Academic Unit: Neurology; Pathology; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
Record Identifier: 9984480348402771

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