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Hypothalamic overexpression of mutant huntingtin causes dysregulation of brown adipose tissue.

Soylu, Rana LU ; Adlesic, Natalie LU ; Baldo, Barbara LU ; Kirik, Deniz LU and Petersén, Åsa LU (2015) In Scientific Reports 5.
Abstract
Expression of mutant huntingtin (htt) protein has been shown to cause metabolic imbalance in animal models of Huntington disease (HD). The pathways involved are not fully understood but dysfunction of both the hypothalamus and brown adipose tissue (BAT) has been implicated. Here we show that targeted expression of mutant HTT in the hypothalamus leads to loss of the A13 dopaminergic cell group located in the zona incerta and reduced mRNA expression of neuropeptide Y1 receptor in the hypothalamus. Furthermore, this is accompanied by downregulation of uncoupling protein 1 expression and PPARγ coactivator-1 alpha in BAT and a rapid body weight gain. Taken together, our data might provide a mechanistic link between expression of mutant HTT,... (More)
Expression of mutant huntingtin (htt) protein has been shown to cause metabolic imbalance in animal models of Huntington disease (HD). The pathways involved are not fully understood but dysfunction of both the hypothalamus and brown adipose tissue (BAT) has been implicated. Here we show that targeted expression of mutant HTT in the hypothalamus leads to loss of the A13 dopaminergic cell group located in the zona incerta and reduced mRNA expression of neuropeptide Y1 receptor in the hypothalamus. Furthermore, this is accompanied by downregulation of uncoupling protein 1 expression and PPARγ coactivator-1 alpha in BAT and a rapid body weight gain. Taken together, our data might provide a mechanistic link between expression of mutant HTT, reduced activity of a hypothalamic dopaminergic pathway and dysfunction of BAT and in part explain the development of an obese phenotype in HD mouse models. (Less)
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author
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Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
5
article number
14598
publisher
Nature Publishing Group
external identifiers
  • pmid:26419281
  • wos:000361952800002
  • scopus:84942898891
  • pmid:26419281
ISSN
2045-2322
DOI
10.1038/srep14598
language
English
LU publication?
yes
id
e30eddf8-498a-44e4-9d78-62e74ee06afc (old id 8160013)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26419281?dopt=Abstract
date added to LUP
2016-04-01 13:30:09
date last changed
2019-11-20 02:40:05
@article{e30eddf8-498a-44e4-9d78-62e74ee06afc,
  abstract     = {Expression of mutant huntingtin (htt) protein has been shown to cause metabolic imbalance in animal models of Huntington disease (HD). The pathways involved are not fully understood but dysfunction of both the hypothalamus and brown adipose tissue (BAT) has been implicated. Here we show that targeted expression of mutant HTT in the hypothalamus leads to loss of the A13 dopaminergic cell group located in the zona incerta and reduced mRNA expression of neuropeptide Y1 receptor in the hypothalamus. Furthermore, this is accompanied by downregulation of uncoupling protein 1 expression and PPARγ coactivator-1 alpha in BAT and a rapid body weight gain. Taken together, our data might provide a mechanistic link between expression of mutant HTT, reduced activity of a hypothalamic dopaminergic pathway and dysfunction of BAT and in part explain the development of an obese phenotype in HD mouse models.},
  author       = {Soylu, Rana and Adlesic, Natalie and Baldo, Barbara and Kirik, Deniz and Petersén, Åsa},
  issn         = {2045-2322},
  language     = {eng},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Hypothalamic overexpression of mutant huntingtin causes dysregulation of brown adipose tissue.},
  url          = {https://lup.lub.lu.se/search/ws/files/3406626/8839751.pdf},
  doi          = {10.1038/srep14598},
  volume       = {5},
  year         = {2015},
}