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Altered Adipocyte Cell Size Distribution Prior to Weight Loss in the R6/2 Model of Huntington's Disease

Dickson, Elna LU ; Fryklund, Claes LU ; Soylu-Kucharz, Rana LU ; Sjögren, Marie LU ; Stenkula, Karin G LU and Björkqvist, Maria LU orcid (2023) In Journal of Huntington's disease 12(3). p.253-266
Abstract

BACKGROUND: Metabolic alterations contribute to disease onset and prognosis of Huntington's disease (HD). Weight loss in the R6/2 mouse model of HD is a consistent feature, with onset in mid-to-late stage of disease.

OBJECTIVE: In the present study, we aimed to investigate molecular and functional changes in white adipose tissue (WAT) that occur at weight loss in R6/2 mice. We further elaborated on the effect of leptin-deficiency and early obesity in R6/2 mice.

METHODS: We performed analyses at 12 weeks of age; a time point that coincides with the start of weight loss in our R6/2 mouse colony. Gonadal (visceral) and inguinal (subcutaneous) WAT depot weights were monitored, as well as adipocyte size distribution. Response to... (More)

BACKGROUND: Metabolic alterations contribute to disease onset and prognosis of Huntington's disease (HD). Weight loss in the R6/2 mouse model of HD is a consistent feature, with onset in mid-to-late stage of disease.

OBJECTIVE: In the present study, we aimed to investigate molecular and functional changes in white adipose tissue (WAT) that occur at weight loss in R6/2 mice. We further elaborated on the effect of leptin-deficiency and early obesity in R6/2 mice.

METHODS: We performed analyses at 12 weeks of age; a time point that coincides with the start of weight loss in our R6/2 mouse colony. Gonadal (visceral) and inguinal (subcutaneous) WAT depot weights were monitored, as well as adipocyte size distribution. Response to isoprenaline-stimulated glycerol release and insulin-stimulated glucose uptake in adipocytes from gonadal WAT was assessed.

RESULTS: In R6/2 mice, WAT depot weights were comparable to wildtype (WT) mice, and the response to insulin and isoprenaline in gonadal adipocytes was unaltered. Leptin-deficient R6/2 mice exhibited distinct changes compared to leptin-deficient WT mice. At 12 weeks, female leptin-deficient R6/2 mice had reduced body weight accompanied by an increased proportion of smaller adipocytes, while in contrast; male mice displayed a shift towards larger adipocyte sizes without a significant body weight reduction at this timepoint.

CONCLUSIONS: We here show that there are early sex-specific changes in adipocyte cell size distribution in WAT of R6/2 mice and leptin-deficient R6/2 mice.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Adipose tissue, body weight, Huntington's disease, leptin, metabolism
in
Journal of Huntington's disease
volume
12
issue
3
pages
14 pages
publisher
IOS Press
external identifiers
  • scopus:85173891250
  • pmid:37718850
ISSN
1879-6397
DOI
10.3233/JHD-230587
language
English
LU publication?
yes
id
7e52653c-659c-4321-9e6d-378b055011db
date added to LUP
2023-10-24 09:25:22
date last changed
2024-04-22 19:20:30
@article{7e52653c-659c-4321-9e6d-378b055011db,
  abstract     = {{<p>BACKGROUND: Metabolic alterations contribute to disease onset and prognosis of Huntington's disease (HD). Weight loss in the R6/2 mouse model of HD is a consistent feature, with onset in mid-to-late stage of disease.</p><p>OBJECTIVE: In the present study, we aimed to investigate molecular and functional changes in white adipose tissue (WAT) that occur at weight loss in R6/2 mice. We further elaborated on the effect of leptin-deficiency and early obesity in R6/2 mice.</p><p>METHODS: We performed analyses at 12 weeks of age; a time point that coincides with the start of weight loss in our R6/2 mouse colony. Gonadal (visceral) and inguinal (subcutaneous) WAT depot weights were monitored, as well as adipocyte size distribution. Response to isoprenaline-stimulated glycerol release and insulin-stimulated glucose uptake in adipocytes from gonadal WAT was assessed.</p><p>RESULTS: In R6/2 mice, WAT depot weights were comparable to wildtype (WT) mice, and the response to insulin and isoprenaline in gonadal adipocytes was unaltered. Leptin-deficient R6/2 mice exhibited distinct changes compared to leptin-deficient WT mice. At 12 weeks, female leptin-deficient R6/2 mice had reduced body weight accompanied by an increased proportion of smaller adipocytes, while in contrast; male mice displayed a shift towards larger adipocyte sizes without a significant body weight reduction at this timepoint.</p><p>CONCLUSIONS: We here show that there are early sex-specific changes in adipocyte cell size distribution in WAT of R6/2 mice and leptin-deficient R6/2 mice.</p>}},
  author       = {{Dickson, Elna and Fryklund, Claes and Soylu-Kucharz, Rana and Sjögren, Marie and Stenkula, Karin G and Björkqvist, Maria}},
  issn         = {{1879-6397}},
  keywords     = {{Adipose tissue; body weight; Huntington's disease; leptin; metabolism}},
  language     = {{eng}},
  month        = {{10}},
  number       = {{3}},
  pages        = {{253--266}},
  publisher    = {{IOS Press}},
  series       = {{Journal of Huntington's disease}},
  title        = {{Altered Adipocyte Cell Size Distribution Prior to Weight Loss in the R6/2 Model of Huntington's Disease}},
  url          = {{http://dx.doi.org/10.3233/JHD-230587}},
  doi          = {{10.3233/JHD-230587}},
  volume       = {{12}},
  year         = {{2023}},
}