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ludc web

Sara Larsson

Research engineer

ludc web

White adipose tissue browning in the R6/2 mouse model of Huntington's disease

Author

  • Andrew C McCourt
  • Lovisa Jakobsson
  • Sara Larsson
  • Cecilia Holm
  • Sarah Piel
  • Eskil Elmér
  • Maria Björkqvist

Summary, in English

Huntington's disease (HD) is a fatal, autosomal dominantly inherited neurodegenerative disorder, characterised not only by progressive cognitive, motor and psychiatric impairments, but also of peripheral pathology. In both human HD and in mouse models of HD there is evidence of increased energy expenditure and weight loss, alongside altered body composition. Unlike white adipose tissue (WAT), brown adipose tissue (BAT), as well as brown-like cells within WAT, expresses the mitochondrial protein, uncoupling protein 1 (UCP1). UCP1 enables dissociation of cellular respiration from ATP utilization, resulting in the release of stored energy as heat. Hyperplasia of brown/beige cells in WAT has been suggested to enhance energy expenditure. In this study, we therefore investigated the gene expression profile, histological appearance, response to cold challenge and functional aspects of WAT in the R6/2 HD mouse model and selected WAT gene expression in the full-length Q175 mouse model of HD. WAT from R6/2 mice contained significantly more brown-like adipocyte regions and had a gene profile suggestive of the presence of brown-like adipocytes, such as higher Ucp1 expression. Cold exposure induced Ucp1 expression in R6/2 inguinal WAT to a markedly higher degree as compared to the thermogenic response in WT WAT. Alongside this, gene expression of transcription factors (Zfp516 and Pparα), important inducers of WAT browning, were increased in R6/2 inguinal WAT, and Creb1 was highlighted as a key transcription factor in HD. In addition to increased WAT Ucp1 expression, a trend towards increased mitochondrial oxygen consumption due to enhanced uncoupling activity was found in inguinal R6/2 WAT. Key gene expressional changes (increased expression of (Zfp516 and Pparα)) were replicated in inguinal WAT obtained from Q175 mice. In summary, for the first time, we here show that HD mouse WAT undergoes a process of browning, resulting in molecular and functional alterations that may contribute to the weight loss and altered metabolism observed with disease progression.

Department/s

  • Molecular Endocrinology
  • Mitochondrial Medicine
  • Clinical Neurophysiology
  • Biomarkers in Brain Disease
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • MultiPark: Multidisciplinary research focused on Parkinson´s disease

Publishing year

2016-08-01

Language

English

Publication/Series

PLoS ONE

Volume

11

Issue

8

Document type

Journal article

Publisher

Public Library of Science

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Molecular Endocrinology
  • Mitochondrial Medicine
  • Biomarkers in Brain Disease

ISBN/ISSN/Other

  • ISSN: 1932-6203