Abstract:
: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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Bochukova EG,Lawler K,Croizier S,Keogh JM,Patel N,Strohbehn G,Lo KK,Humphrey J,Hokken-Koelega A,Damen L,Donze S,Bouret SG,Plagnol V,Farooqi ISdoi
10.1016/j.celrep.2018.03.018subject
Has Abstractpub_date
2018-03-27 00:00:00pages
3401-3408issue
13issn
2211-1247pii
S2211-1247(18)30347-4journal_volume
22pub_type
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