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Hypothalamic overexpression of mutant huntingtin causes dysregulation of brown adipose tissue

Soylu-Kucharz R1, Adlesic N1, Baldo B1, Kirik D2 and Petersén Å1.

1Translational Neuroendocrine Research Unit, Department of Experimental Medical Sciences, Lund University, Sweden.
2Brain Repair and Imaging in Neural Systems (B.R.A.I.N.S.) Unit, Department of Experimental Medical Sciences Lund University, Sweden.

Sci Rep. Sep 30;5:14598 (2015)


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.