Hypothalamic overexpression of mutant huntingtin causes dysregulation of brown adipose tissue.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8160013
- author
- Soylu, Rana LU ; Adlesic, Natalie LU ; Baldo, Barbara LU ; Kirik, Deniz LU and Petersén, Åsa LU
- organization
- publishing date
- 2015
- type
- 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
- 2022-04-14 01:31:04
@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/files/3406626/8839751.pdf}},
doi = {{10.1038/srep14598}},
volume = {{5}},
year = {{2015}},
}