The Drosophila ETV5 Homologue Ets96B: Molecular Link between Obesity and Bipolar Disorder.
Several reports suggest obesity and bipolar disorder (BD) share some physiological and behavioural similarities. For instance, obese individuals are more impulsive and have heightened reward responsiveness, phenotypes associated with BD, while bipolar patients become obese at a higher rate and earli...
Main Authors: | , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2016-06-01
|
Series: | PLoS Genetics |
Online Access: | http://europepmc.org/articles/PMC4900636?pdf=render |
id |
doaj-41cabc02c7534b94aaf1b052bd893860 |
---|---|
record_format |
Article |
spelling |
doaj-41cabc02c7534b94aaf1b052bd8938602020-11-25T02:49:24ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042016-06-01126e100610410.1371/journal.pgen.1006104The Drosophila ETV5 Homologue Ets96B: Molecular Link between Obesity and Bipolar Disorder.Michael J WilliamsAnica KlockarsAnders ErikssonSarah VoisinRohit DnyansagarLyle WiemerslageAnna KasagiannisMehwish AkramSania KhederValerie AmbrosiEmilie HallqvistRobert FredrikssonHelgi B SchiöthSeveral reports suggest obesity and bipolar disorder (BD) share some physiological and behavioural similarities. For instance, obese individuals are more impulsive and have heightened reward responsiveness, phenotypes associated with BD, while bipolar patients become obese at a higher rate and earlier age than people without BD; however, the molecular mechanisms of such an association remain obscure. Here we demonstrate, using whole transcriptome analysis, that Drosophila Ets96B, homologue of obesity-linked gene ETV5, regulates cellular systems associated with obesity and BD. Consistent with a role in obesity and BD, loss of nervous system Ets96B during development increases triacylglyceride concentration, while inducing a heightened startle-response, as well as increasing hyperactivity and reducing sleep. Of notable interest, mouse Etv5 and Drosophila Ets96B are expressed in dopaminergic-rich regions, and loss of Ets96B specifically in dopaminergic neurons recapitulates the metabolic and behavioural phenotypes. Moreover, our data indicate Ets96B inhibits dopaminergic-specific neuroprotective systems. Additionally, we reveal that multiple SNPs in human ETV5 link to body mass index (BMI) and BD, providing further evidence for ETV5 as an important and novel molecular intermediate between obesity and BD. We identify a novel molecular link between obesity and bipolar disorder. The Drosophila ETV5 homologue Ets96B regulates the expression of cellular systems with links to obesity and behaviour, including the expression of a conserved endoplasmic reticulum molecular chaperone complex known to be neuroprotective. Finally, a connection between the obesity-linked gene ETV5 and bipolar disorder emphasizes a functional relationship between obesity and BD at the molecular level.http://europepmc.org/articles/PMC4900636?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Michael J Williams Anica Klockars Anders Eriksson Sarah Voisin Rohit Dnyansagar Lyle Wiemerslage Anna Kasagiannis Mehwish Akram Sania Kheder Valerie Ambrosi Emilie Hallqvist Robert Fredriksson Helgi B Schiöth |
spellingShingle |
Michael J Williams Anica Klockars Anders Eriksson Sarah Voisin Rohit Dnyansagar Lyle Wiemerslage Anna Kasagiannis Mehwish Akram Sania Kheder Valerie Ambrosi Emilie Hallqvist Robert Fredriksson Helgi B Schiöth The Drosophila ETV5 Homologue Ets96B: Molecular Link between Obesity and Bipolar Disorder. PLoS Genetics |
author_facet |
Michael J Williams Anica Klockars Anders Eriksson Sarah Voisin Rohit Dnyansagar Lyle Wiemerslage Anna Kasagiannis Mehwish Akram Sania Kheder Valerie Ambrosi Emilie Hallqvist Robert Fredriksson Helgi B Schiöth |
author_sort |
Michael J Williams |
title |
The Drosophila ETV5 Homologue Ets96B: Molecular Link between Obesity and Bipolar Disorder. |
title_short |
The Drosophila ETV5 Homologue Ets96B: Molecular Link between Obesity and Bipolar Disorder. |
title_full |
The Drosophila ETV5 Homologue Ets96B: Molecular Link between Obesity and Bipolar Disorder. |
title_fullStr |
The Drosophila ETV5 Homologue Ets96B: Molecular Link between Obesity and Bipolar Disorder. |
title_full_unstemmed |
The Drosophila ETV5 Homologue Ets96B: Molecular Link between Obesity and Bipolar Disorder. |
title_sort |
drosophila etv5 homologue ets96b: molecular link between obesity and bipolar disorder. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Genetics |
issn |
1553-7390 1553-7404 |
publishDate |
2016-06-01 |
description |
Several reports suggest obesity and bipolar disorder (BD) share some physiological and behavioural similarities. For instance, obese individuals are more impulsive and have heightened reward responsiveness, phenotypes associated with BD, while bipolar patients become obese at a higher rate and earlier age than people without BD; however, the molecular mechanisms of such an association remain obscure. Here we demonstrate, using whole transcriptome analysis, that Drosophila Ets96B, homologue of obesity-linked gene ETV5, regulates cellular systems associated with obesity and BD. Consistent with a role in obesity and BD, loss of nervous system Ets96B during development increases triacylglyceride concentration, while inducing a heightened startle-response, as well as increasing hyperactivity and reducing sleep. Of notable interest, mouse Etv5 and Drosophila Ets96B are expressed in dopaminergic-rich regions, and loss of Ets96B specifically in dopaminergic neurons recapitulates the metabolic and behavioural phenotypes. Moreover, our data indicate Ets96B inhibits dopaminergic-specific neuroprotective systems. Additionally, we reveal that multiple SNPs in human ETV5 link to body mass index (BMI) and BD, providing further evidence for ETV5 as an important and novel molecular intermediate between obesity and BD. We identify a novel molecular link between obesity and bipolar disorder. The Drosophila ETV5 homologue Ets96B regulates the expression of cellular systems with links to obesity and behaviour, including the expression of a conserved endoplasmic reticulum molecular chaperone complex known to be neuroprotective. Finally, a connection between the obesity-linked gene ETV5 and bipolar disorder emphasizes a functional relationship between obesity and BD at the molecular level. |
url |
http://europepmc.org/articles/PMC4900636?pdf=render |
work_keys_str_mv |
AT michaeljwilliams thedrosophilaetv5homologueets96bmolecularlinkbetweenobesityandbipolardisorder AT anicaklockars thedrosophilaetv5homologueets96bmolecularlinkbetweenobesityandbipolardisorder AT anderseriksson thedrosophilaetv5homologueets96bmolecularlinkbetweenobesityandbipolardisorder AT sarahvoisin thedrosophilaetv5homologueets96bmolecularlinkbetweenobesityandbipolardisorder AT rohitdnyansagar thedrosophilaetv5homologueets96bmolecularlinkbetweenobesityandbipolardisorder AT lylewiemerslage thedrosophilaetv5homologueets96bmolecularlinkbetweenobesityandbipolardisorder AT annakasagiannis thedrosophilaetv5homologueets96bmolecularlinkbetweenobesityandbipolardisorder AT mehwishakram thedrosophilaetv5homologueets96bmolecularlinkbetweenobesityandbipolardisorder AT saniakheder thedrosophilaetv5homologueets96bmolecularlinkbetweenobesityandbipolardisorder AT valerieambrosi thedrosophilaetv5homologueets96bmolecularlinkbetweenobesityandbipolardisorder AT emiliehallqvist thedrosophilaetv5homologueets96bmolecularlinkbetweenobesityandbipolardisorder AT robertfredriksson thedrosophilaetv5homologueets96bmolecularlinkbetweenobesityandbipolardisorder AT helgibschioth thedrosophilaetv5homologueets96bmolecularlinkbetweenobesityandbipolardisorder AT michaeljwilliams drosophilaetv5homologueets96bmolecularlinkbetweenobesityandbipolardisorder AT anicaklockars drosophilaetv5homologueets96bmolecularlinkbetweenobesityandbipolardisorder AT anderseriksson drosophilaetv5homologueets96bmolecularlinkbetweenobesityandbipolardisorder AT sarahvoisin drosophilaetv5homologueets96bmolecularlinkbetweenobesityandbipolardisorder AT rohitdnyansagar drosophilaetv5homologueets96bmolecularlinkbetweenobesityandbipolardisorder AT lylewiemerslage drosophilaetv5homologueets96bmolecularlinkbetweenobesityandbipolardisorder AT annakasagiannis drosophilaetv5homologueets96bmolecularlinkbetweenobesityandbipolardisorder AT mehwishakram drosophilaetv5homologueets96bmolecularlinkbetweenobesityandbipolardisorder AT saniakheder drosophilaetv5homologueets96bmolecularlinkbetweenobesityandbipolardisorder AT valerieambrosi drosophilaetv5homologueets96bmolecularlinkbetweenobesityandbipolardisorder AT emiliehallqvist drosophilaetv5homologueets96bmolecularlinkbetweenobesityandbipolardisorder AT robertfredriksson drosophilaetv5homologueets96bmolecularlinkbetweenobesityandbipolardisorder AT helgibschioth drosophilaetv5homologueets96bmolecularlinkbetweenobesityandbipolardisorder |
_version_ |
1724743731170508800 |