Chronic effects of AJ-9677 on energy expenditure and energy source utilization in rats

The effects of AJ-9677 on metabolic parameters were examined in rats that had or had not been chronically treated with this beta3-adrenoceptor agonist. A challenge administration of AJ-9677 increased both the temperature of brown adipose tissue and energy expenditure in both groups of rats. However, whereas the former effect was subject to desensitization, the latter effect was augmented by prior chronic administration of AJ-9677. Whereas a challenge administration of AJ-9677 induced a decrease in the respiratory quotient that persisted for at least 15 h in rats pretreated with vehicle, the initial decrease in this parameter lasted for only 4 h in rats pretreated with AJ-9677. These results suggest that, in rats subjected to chronic treatment with AJ-9677, a challenge administration of this drug increased energy expenditure by stimulation not only of fat oxidation but also of glucose oxidation.