UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

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

Bochukova, EG; Lawler, K; Croizier, S; Keogh, JM; Patel, N; Strohbehn, G; Lo, KK; ... Farooqi, IS; + view all (2018) A Transcriptomic Signature of the Hypothalamic Response to Fasting and BDNF Deficiency in Prader-Willi Syndrome. Cell Reports , 22 (13) pp. 3401-3408. 10.1016/j.celrep.2018.03.018. Green open access

[thumbnail of Published article]
Preview
Text (Published article)
Bochukova_Trascriptomic.pdf - Published Version

Download (3MB) | Preview
[thumbnail of Supplementary files] Archive (Supplementary files)
1-s2.0-S2211124718303474-suppl.zip

Download (47MB)

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.

Type: Article
Title: A Transcriptomic Signature of the Hypothalamic Response to Fasting and BDNF Deficiency in Prader-Willi Syndrome
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2018.03.018
Publisher version: https://doi.org/10.1016/j.celrep.2018.03.018
Language: English
Additional information: Copyright © 2018 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: hypothalamus, Prader-Willi syndrome, BDNF, Agrp, obesity, SNORD116
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: https://discovery.ucl.ac.uk/id/eprint/10053034
Downloads since deposit
59Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item