Leptin deficiency reverses high metabolic state and weight loss without affecting central pathology in the R6/2 mouse model of Huntington's disease

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Body weight has been shown to be a predictor of clinical progression in Huntington's disease (HD). Alongside widespread neuronal pathology, both HD patients and the R6/2 mouse model of HD exhibit weight loss and increased energy expenditure, providing a rationale for targeting whole-body energy metabolism in HD. Leptin-deficient mice display low energy expenditure and increased body weight. We therefore hypothesized that normalizing energy metabolism in R6/2 mice, utilizing leptin- deficiency, would lead to a slower disease progression in the R6/2 mouse. In this study, we show that R6/2 mice on a leptin-deficient genetic background display increased body weight and increased fat mass compared to R6/2 mice, as well as wild type littermates. The increased body weight was accompanied by low energy expenditure, illustrated by a reduction in respiratory exchange rate. Leptin-deficient R6/2 mice had large white adipocytes with white adipocyte gene expression characteristics, in contrast to white adipose tissue in R6/2 mice, where white adipose tissue showed signs of browning. Leptin-deficient R6/2 mice did not exhibit improved neuropathological measures. Our results indicate that lowering energy metabolism in HD, by increasing fat mass and reducing respiratory exchange rate, is not sufficient to affect neuropathology. Further studies targeting energy metabolism in HD are warranted.

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • Sahlgrenska University Hospital
  • University College London
  • Göteborgs universitet
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Neurologi

Nyckelord

Originalspråkengelska
Artikelnummer104560
TidskriftNeurobiology of Disease
Volym132
StatusPublished - 2019
PublikationskategoriForskning
Peer review utfördJa

Relaterad forskningsoutput

Marie Sjögren, 2019, Lund: Lund University, Faculty of Medicine. 115 s.

Forskningsoutput: AvhandlingDoktorsavhandling (monografi)

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