We have reported that chronic treatment with beta3-adrenoceptor agonists reduces body fat content and induces the expression of mitochondrial thermogenic
uncoupling protein 1 (UCP1) in adipose tissue in the dog. To evaluate the role of UCP1 in the anti-
obesity effect of the agonists, we isolated adipocytes from subcutaneous fat pad of beagles before and after a 2-week treatment with
AJ-9677, a specific beta3-adrenoceptor agonist, and examined their thermogenic activity in vitro. Histological and
protein analysis revealed that adipose tissues before the treatment were composed of unilocular cells filled with a single large droplet, while the tissues after the treatment contained many smaller and some multilocular adipocytes expressing UCP1 and abundant
mitochondrial proteins. Before the treatment, oxygen consumption rate was very low and did not change even when the cells were stimulated by
AJ-9677. Two-week
AJ-9677 treatment increased basal oxygen consumption rate by 7-fold, and produced a clear responsiveness to
AJ-9677 stimulation. Thus, chronic treatment with
AJ-9677 induced UCP1 in adipocytes, where oxygen consumption increased in response to
AJ-9677 stimulation. It was suggested that UCP1-dependent energy expenditure in adipose tissue contributes to the anti-
obesity effect of beta3-adrenoceptor agonist in dogs.