Increased fat mass in androgen receptor knockout mice is caused by decreased physical activity with no change in food consumption
Jeffrey Zajac, K Rana, B Fam, S Andrikopoulos & Helen MacLean
We have used an androgen receptor knockout (ARKO) mouse model with an in-frame deletion of the 2nd zinc finger of the DNA binding domain, which abolishes the genomic actions of the AR to investigate androgen regulation of fat mass. At 12 weeks of age, ARKO males have increased adiposity compared to wildtype (WT) males, with subcutaneous fat mass increased by 75% (P<0.001, n≥17/group) and infrarenal fat mass increased by 36% (P<0.05, n≥17/group). However, total body mass of ARKO males is decreased by 13% versus WT males (P<0.001, n≥17/group) at 12 and 30 weeks of age. Mean voluntary physical activity at 12 weeks, measured by wheel running, is 86% lower in ARKO mice (P<0.05, n=34/group). At 24 weeks of age, following 12 weeks of a high fat diet (containing 60% fat), total body mass is not different between WT and ARKO mice (n=1112/group). Subcutaneous fat mass remains increased by 66% compared to WT males (P<0.001, n=1112/group), however there is no difference in infrarenal fat mass. Average weekly food intake is not different, but mean voluntary physical activity is decreased by 49% in ARKO males compared to WT males (P<0.001, n=1112/group). There is no difference in resting energy expenditure, fat oxidation or glucose oxidation rates between the two groups (n=11/group). This study suggests that increased adiposity in ARKO mice is in part due to decreased voluntary physical activity but not increased food consumption or decreased resting energy expenditure.