Bibliographic Details
| Title: |
Brainstem BDNF neurons are downstream of GFRAL/GLP1R signalling. |
| Authors: |
Feetham, Claire H., Collabolletta, Valeria, Worth, Amy A., Shoop, Rosemary, Groom, Sam, Harding, Court, Boutagouga Boudjadja, Mehdi, Coskun, Tamer, Emmerson, Paul J., D'Agostino, Giuseppe, Luckman, Simon M. |
| Source: |
Nature Communications; 12/30/2024, Vol. 15 Issue 1, p1-16, 16p |
| Subject Terms: |
GROWTH differentiation factors, BRAIN-derived neurotrophic factor, FATTY acid oxidation, SOLITARY nucleus, MEDICAL sciences |
| 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. The major site of action for obesity treatments based on GLP1R agonists is at the level of the brainstem where neurons share receptors for GLP-1 and GFRAL. Here, authors show two pathways downstream of GFRAL neurons, which are required for the weight-reducing actions of GDF15 and GLP1RA. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
