Background Besides neurological symptoms, HD-patients show metabolic changes in early stages of the disease, such as alterations in glucose metabolism and reduced peripheral insulin sensitivity. The exact mechanisms of the metabolic changes are unclear. One possible target might be the insulin sensitive glucose transporter 4 (GLUT4), which is responsible for glucose uptake in muscle and adipose tissue.
Aim Differences in GLUT4 expression and distribution in white adipose tissue (WAT) of transgenic R6/2 mice and wild type mice were studied. In addition glucose uptake assays were used to investigate the effect of changes in expression and distribution on the glucose uptake in adipocytes.
Methods Western blot analysis were used to compare GLUT4 expression in WAT between the R6/2 mouse model and wild type. Subfractionated organculture samples were used to determine the insulin induced GLUT4 translocation to the plasma membrane (PM). Preadipocytes were isolated from R6/2 mice and wild type and differentiated to primary adipocytes. The adipocytes were used to measure basal and insulin stimulated glucose uptake (glucose uptake assay with C14 marked desoxyglucose). In addition, differentiation ratio and triglyceride content were determined.
Results GLUT4 expression is significantly increased in WAT of R6/2 mice compared to wild type mice at the age of 12 weeks. The basal GLUT4 content in the PM-fraction of R6/2 mice is elevated and insulin leads to a pronounced translocation to the PM compared to wild type. Adipocytes derived from R6/2 mice show reduced differentiation ratios and lower triglyceride content. The basal and insulin stimulated glucose-uptake is significantly higher in primary adipocytes isolated from R6/2 mice compared to wild type adipocytes.
Conclusion The R6/2 mouse model shows alterations of GLUT4 expression and intracellular localisation in WAT. The higher GLUT4 expression and the higher content in the PM lead to an increased basal and insulin stimulated glucose uptake in R6/2-derived adipocytes. In addition, lower differentiation ratios and triglyceride content might be due to an impairment in adipogenic differentiation.
- R6/2 mouse model
- white adipose tissue
- glucose metabolism
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