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

Article type: Research Article

Authors: Dickson, Elna^a | Fryklund, Claes^b | Soylu-Kucharz, Rana^a | Sjögren, Marie^a | Stenkula, Karin G.^b | Björkqvist, Maria^{a; *}

Affiliations: [a] Brain Disease Biomarker Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden | [b] Glucose Transport and Protein Trafficking, Department of Experimental Medical Science, Lund University, Lund, Sweden

Correspondence: [*] Correspondence to: Maria Björkqvist, Brain Disease Biomarker Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, BMC A10, Lund University, 22184 Lund, Sweden. Tel.: +46 72 700 71 63; E-mail: [email protected].

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 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.

Keywords: Adipose tissue, body weight, Huntington’s disease, leptin, metabolism

DOI: 10.3233/JHD-230587

Journal: Journal of Huntington's Disease, vol. 12, no. 3, pp. 253-266, 2023