The locus coeruleus contributes to the anorectic, nausea, and autonomic physiological effects of glucagon-like peptide-1
Increasing the therapeutic potential and reducing the side effects of U.S. Food and Drug Administration-approved glucagon-like peptide-1 receptor (GLP-1R) agonists used to treat obesity require complete characterization of the central mechanisms that mediate both the food intake-suppressive and illness-like effects of GLP-1R signaling. Our studies, in the rat, demonstrate that GLP-1Rs in the locus coeruleus (LC) are pharmacologically and physiologically relevant for food intake control. Furthermore, agonism of LC GLP-1Rs induces illness-like behaviors, and antagonism of LC GLP-1Rs can attenuate GLP-1R-mediated nausea. Electrophysiological and behavioral pharmacology data support a role for LC GLP-1Rs expressed on presynaptic glutamatergic terminals in the control of feeding and malaise. Collectively, our work establishes the LC as a site of action for GLP-1 signaling and extends our understanding of the GLP-1 signaling mechanism necessary for the development of improved obesity pharmacotherapies.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
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| Enthalten in: |
Science advances - 9(2023), 38 vom: 22. Sept., Seite eadh0980 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Fortin, Samantha M [VerfasserIn] |
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| Links: |
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| Themen: |
89750-14-1 |
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| Anmerkungen: |
Date Completed 22.09.2023 Date Revised 19.10.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1126/sciadv.adh0980 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM362262136 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Increasing the therapeutic potential and reducing the side effects of U.S. Food and Drug Administration-approved glucagon-like peptide-1 receptor (GLP-1R) agonists used to treat obesity require complete characterization of the central mechanisms that mediate both the food intake-suppressive and illness-like effects of GLP-1R signaling. Our studies, in the rat, demonstrate that GLP-1Rs in the locus coeruleus (LC) are pharmacologically and physiologically relevant for food intake control. Furthermore, agonism of LC GLP-1Rs induces illness-like behaviors, and antagonism of LC GLP-1Rs can attenuate GLP-1R-mediated nausea. Electrophysiological and behavioral pharmacology data support a role for LC GLP-1Rs expressed on presynaptic glutamatergic terminals in the control of feeding and malaise. Collectively, our work establishes the LC as a site of action for GLP-1 signaling and extends our understanding of the GLP-1 signaling mechanism necessary for the development of improved obesity pharmacotherapies | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Petticord, Marisa C |e verfasserin |4 aut | |
| 700 | 1 | |a Ragozzino, Forrest J |e verfasserin |4 aut | |
| 700 | 1 | |a Peters, James H |e verfasserin |4 aut | |
| 700 | 1 | |a Hayes, Matthew R |e verfasserin |4 aut | |
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