A Transcriptomic Signature of the Hypothalamic Response to Fasting and BDNF Deficiency in Prader-Willi Syndrome.

Détails

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Etat: Public
Version: Final published version
ID Serval
serval:BIB_4EFEF663B5E3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
A Transcriptomic Signature of the Hypothalamic Response to Fasting and BDNF Deficiency in Prader-Willi Syndrome.
Périodique
Cell Reports
Auteur⸱e⸱s
Bochukova E.G., Lawler K., Croizier S., Keogh J.M., Patel N., Strohbehn G., Lo K.K., Humphrey J., Hokken-Koelega A., Damen L., Donze S., Bouret S.G., Plagnol V., Farooqi I.S.
ISSN
2211-1247 (Electronic)
Statut éditorial
Publié
Date de publication
2018
Peer-reviewed
Oui
Volume
22
Numéro
13
Pages
3401-3408
Langue
anglais
Résumé
Transcriptional analysis of brain tissue from people with molecularly defined causes of obesity may highlight disease mechanisms and therapeutic targets. We performed RNA sequencing of hypothalamus from individuals with Prader-Willi syndrome (PWS), a genetic obesity syndrome characterized by severe hyperphagia. We found that upregulated genes overlap with the transcriptome of mouse Agrp neurons that signal hunger, while downregulated genes overlap with the expression profile of Pomc neurons activated by feeding. Downregulated genes are expressed mainly in neuronal cells and contribute to neurogenesis, neurotransmitter release, and synaptic plasticity, while upregulated, predominantly microglial genes are involved in inflammatory responses. This transcriptional signature may be mediated by reduced brain-derived neurotrophic factor expression. Additionally, we implicate disruption of alternative splicing as a potential molecular mechanism underlying neuronal dysfunction in PWS. Transcriptomic analysis of the human hypothalamus may identify neural mechanisms involved in energy homeostasis and potential therapeutic targets for weight loss.

Mots-clé
Agrp, BDNF, Prader-Willi syndrome, SNORD116, hypothalamus, obesity
Pubmed
Web of science
Open Access
Oui
Création de la notice
29/03/2018 17:36
Dernière modification de la notice
20/08/2019 15:04
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