Brainstem BDNF neurons are downstream of GFRAL/GLP1R signalling
Abstract Growth differentiation factor 15, GDF15, and glucagon-like peptide-1 (GLP-1) analogues act through brainstem neurons that co-localise their receptors, GDNF-family receptor α-like (GFRAL) and GLP1R, to reduce food intake and body weight. However, their use as clinical treatments is partially...
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Nature Portfolio
2024-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54367-y |
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| author | Claire H. Feetham Valeria Collabolletta Amy A. Worth Rosemary Shoop Sam Groom Court Harding Mehdi Boutagouga Boudjadja Tamer Coskun Paul J. Emmerson Giuseppe D’Agostino Simon M. Luckman |
| author_facet | Claire H. Feetham Valeria Collabolletta Amy A. Worth Rosemary Shoop Sam Groom Court Harding Mehdi Boutagouga Boudjadja Tamer Coskun Paul J. Emmerson Giuseppe D’Agostino Simon M. Luckman |
| author_sort | Claire H. Feetham |
| collection | DOAJ |
| description | Abstract Growth differentiation factor 15, GDF15, and glucagon-like peptide-1 (GLP-1) analogues act through brainstem neurons that co-localise their receptors, GDNF-family receptor α-like (GFRAL) and GLP1R, to reduce food intake and body weight. However, their use as clinical treatments is partially hampered since both can also induce sickness-like behaviours, including aversion, that are mediated through a well-characterised pathway via the exterolateral parabrachial nucleus. Here, in mice, we describe a separate pathway downstream of GFRAL/GLP1R neurons that involves a distinct population of brain-derived neurotrophic factor (BDNF) cells in the medial nucleus of the tractus solitarius. Thus, BDNFmNTS neurons are required for the weight-reducing actions of both GDF15 and the GLP1RA, Exendin-4. Moreover, acute activation of BDNFmNTS neurons is sufficient to reduce food intake and drive fatty acid oxidation and might provide a route for longer-term weight loss. |
| format | Article |
| id | doaj-art-9b68f8a4756e46799bb63c6c72b97dea |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-9b68f8a4756e46799bb63c6c72b97dea2025-01-05T12:35:27ZengNature PortfolioNature Communications2041-17232024-12-0115111610.1038/s41467-024-54367-yBrainstem BDNF neurons are downstream of GFRAL/GLP1R signallingClaire H. Feetham0Valeria Collabolletta1Amy A. Worth2Rosemary Shoop3Sam Groom4Court Harding5Mehdi Boutagouga Boudjadja6Tamer Coskun7Paul J. Emmerson8Giuseppe D’Agostino9Simon M. Luckman10Faculty of Biology, Medicine and Health, University of ManchesterFaculty of Biology, Medicine and Health, University of ManchesterFaculty of Biology, Medicine and Health, University of ManchesterFaculty of Biology, Medicine and Health, University of ManchesterFaculty of Biology, Medicine and Health, University of ManchesterFaculty of Biology, Medicine and Health, University of ManchesterFaculty of Biology, Medicine and Health, University of ManchesterLilly Research Laboratories, Eli Lilly & CompanyLilly Research Laboratories, Eli Lilly & CompanyFaculty of Biology, Medicine and Health, University of ManchesterFaculty of Biology, Medicine and Health, University of ManchesterAbstract Growth differentiation factor 15, GDF15, and glucagon-like peptide-1 (GLP-1) analogues act through brainstem neurons that co-localise their receptors, GDNF-family receptor α-like (GFRAL) and GLP1R, to reduce food intake and body weight. However, their use as clinical treatments is partially hampered since both can also induce sickness-like behaviours, including aversion, that are mediated through a well-characterised pathway via the exterolateral parabrachial nucleus. Here, in mice, we describe a separate pathway downstream of GFRAL/GLP1R neurons that involves a distinct population of brain-derived neurotrophic factor (BDNF) cells in the medial nucleus of the tractus solitarius. Thus, BDNFmNTS neurons are required for the weight-reducing actions of both GDF15 and the GLP1RA, Exendin-4. Moreover, acute activation of BDNFmNTS neurons is sufficient to reduce food intake and drive fatty acid oxidation and might provide a route for longer-term weight loss.https://doi.org/10.1038/s41467-024-54367-y |
| spellingShingle | Claire H. Feetham Valeria Collabolletta Amy A. Worth Rosemary Shoop Sam Groom Court Harding Mehdi Boutagouga Boudjadja Tamer Coskun Paul J. Emmerson Giuseppe D’Agostino Simon M. Luckman Brainstem BDNF neurons are downstream of GFRAL/GLP1R signalling Nature Communications |
| title | Brainstem BDNF neurons are downstream of GFRAL/GLP1R signalling |
| title_full | Brainstem BDNF neurons are downstream of GFRAL/GLP1R signalling |
| title_fullStr | Brainstem BDNF neurons are downstream of GFRAL/GLP1R signalling |
| title_full_unstemmed | Brainstem BDNF neurons are downstream of GFRAL/GLP1R signalling |
| title_short | Brainstem BDNF neurons are downstream of GFRAL/GLP1R signalling |
| title_sort | brainstem bdnf neurons are downstream of gfral glp1r signalling |
| url | https://doi.org/10.1038/s41467-024-54367-y |
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