Background In addition to classical neurological symptoms, Huntington’s disease (HD) is complicated by peripheral pathology, including weight loss, altered body composition and skeletal muscle wasting. Both the mutant gene and protein are expressed in cells and tissues throughout the body. Changes in gene expression in the brain, blood and peripheral tissues have been shown in human HD as well as in HD mice. HD mice exhibit early disruption of adipose tissue (AT) storage mechanisms and HD mouse adipocytes have been shown to acquire a de-differentiated phenotype, characterised by impaired expression of fat storage genes.

Aims We propose that human AT may be a useful model with which to investigate molecular pathways of HD. The goal of this study is to demonstrate that adipose tissue can provide an understanding of HD specific molecular changes and further, can be used to identify HD-related gene expression signatures.

Methods/techniques Subcutaneous AT biopsies were obtained from premanifest HD gene carriers, stage II/III HD patients and control subjects. Samples were snap frozen and subsequently, RNA was extracted. Gene expression analysis was performed using Affymetrix GeneChip^®Human Gene 1.0 ST Array and RT-qPCR. A SAM analysis was performed to identify significantly differentially expressed genes between groups and pathway analyses were performed with MetaCoreTM pathway analysis software.

Results/outcome Principal components analysis reveals a distinction between control and premanifest HD groups. Pathway analysis suggests alterations in fatty acid metabolism pathways, angiotensin signalling pathways and immune pathways in HD adipose tissue.

Conclusions Our data suggests that studying gene expression changes in AT could provide an understanding of HD specific molecular changes and the knowledge obtained could offer valuable insight into HD pathology, as well as translate into potential disease markers.