Effects of daipose-specific glucose transporter type 4 expression on glucose homeostasis mediated through alterations in adipose tissue composition
Dwyer, Peter M.
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Objective: Rates of obesity are rising in the U.S. and on a global scale. With this increasing incidence of obesity we are seeing an accompanying rise in the pathologies associated with type II diabetes mellitus (DMII) such as altered insulin sensitivity and glucose homeostasis. The notion of the adipocyte as a biologically dynamic cell is becoming more prevalent and recent evidence implicates the adipocyte as a key regulator in the onset of the aforementioned pathologies. The aim of this study is to further elucidate how changes in the expression of glucose transporter type 4 (GLUT4) in adipocytes may alter adipose tissue function and biology, specifically, if and how these alterations may affect downstream metabolic functions such as glucose uptake. Methods: Male and female adipose-specific GLUT4 overexpressor (AG40x) mice along with wild type (WT) littermates were monitored for changes in weight, body fat percentage, glucose tolerance and adipocyte metabolism over a period of 10-18 weeks. Additional cohorts of the transgenic and WT animals were also treated with a high energy diet to exacerbate any potential differences. Results: AG40x animals on a balanced diet showed high glucose clearance rates compared to WT animals; however, the high energy diet impaired glucose clearance for the AG40x animals. Overexpression of GLUT4 in adipose promotes increased weight gain and fat deposition but does not significantly alter adipose tissue composition compared to the WT balanced diet animals. Conclusion: Although overexpression of GLUT4 in adipose tissue appears to bring about undesired effects of weight gain, these animals were protected from adverse weight gain when challenged with a high energy diet. In both transgenic study groups, fat percentages are increased although adipose composition tissue was no significantly altered as seen in WT high-energy diet animals. This may contribute to the improved glucose clearance profiles seen in this particular model suggesting a potential therapeutic target for those who are high risk for DMII.
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