Altered Adipocyte Cell Size Distribution Prior to Weight Loss in the R6/2 Model of Huntington's Disease
(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
- Dickson, Elna LU ; Fryklund, Claes LU ; Soylu-Kucharz, Rana LU ; Sjögren, Marie LU ; Stenkula, Karin G LU and Björkqvist, Maria LU
- organization
-
- MultiPark: Multidisciplinary research focused on Parkinson´s disease
- Biomarkers in Brain Disease (research group)
- Department of Experimental Medical Science
- Wallenberg Neuroscience Centre, Lund
- Glucose Transport and Protein Trafficking (research group)
- EXODIAB: Excellence of Diabetes Research in Sweden
- publishing date
- 2023-10-03
- 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
- 2024-07-16 04:02:34
@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}}, }