serval:BIB_4EFEF663B5E3
A Transcriptomic Signature of the Hypothalamic Response to Fasting and BDNF Deficiency in Prader-Willi Syndrome.
10.1016/j.celrep.2018.03.018
000428396300004
29590610
Bochukova
E.G.
author
Lawler
K.
author
Croizier
S.
author
Keogh
J.M.
author
Patel
N.
author
Strohbehn
G.
author
Lo
K.K.
author
Humphrey
J.
author
Hokken-Koelega
A.
author
Damen
L.
author
Donze
S.
author
Bouret
S.G.
author
Plagnol
V.
author
Farooqi
I.S.
author
article
2018
Cell Reports
2211-1247
journal
22
13
3401-3408
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.
Agrp
BDNF
Prader-Willi syndrome
SNORD116
hypothalamus
obesity
eng
60_published
true
peer-reviewed
University of Lausanne
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