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

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 PPARĪ³ 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.
AuthorsRana Soylu-Kucharz, Natalie Adlesic, Barbara Baldo, Deniz Kirik, Åsa Petersén
JournalScientific reports (Sci Rep) Vol. 5 Pg. 14598 (Sep 30 2015) ISSN: 2045-2322 [Electronic] England
PMID26419281 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Htt protein, mouse
  • Huntingtin Protein
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Tyrosine 3-Monooxygenase
Topics
  • Adipose Tissue, Brown (metabolism)
  • Animals
  • Cell Count
  • Dependovirus (genetics)
  • Dopaminergic Neurons (metabolism)
  • Gene Expression
  • Genetic Vectors (administration & dosage, genetics)
  • Huntingtin Protein
  • Hypothalamus (metabolism, pathology)
  • Immunohistochemistry
  • Mice
  • Mutation
  • Nerve Tissue Proteins (genetics)
  • Neurons (metabolism)
  • Nuclear Proteins (genetics)
  • Phenotype
  • Time Factors
  • Transgenes
  • Tyrosine 3-Monooxygenase (genetics, metabolism)

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