Exercise training and drug treatment
Male C57B/6J Mice (8 wks old) were randomly divided into 4 cohorts comprising (i) vehicle-treated & sedentary (V), (ii) GW1516-treated & sedentary (GW), (iii) vehicle-treated & exercise trained (Tr) and (iv) GW1516-treated & exercise trained (Tr+GW) (N=9). Mice in all groups were acclimated to moderate treadmill running (10 m/min for 15 min) every other day for 1 week. After acclimation, basal running endurances for the 4 groups were determined using a treadmill running test, where the speed was gradually increased from 0 to 15 m/min and then maintained constant until exhaustion (Week 0). Following the initial test, the mice in the exercise groups were subjected to 4 weeks (5 days/week) of exercise training. The mice were trained on a treadmill inclined at 5 degrees, with progressively increasing intensity and time. At the end of 4 weeks, all exercise-trained mice were running for 50 min/day at 18 m/min. During the 4 weeks, mice from both the sedentary and trained groups were either treated with vehicle or GW1516 (5 mg/kg/day). At the end of the drug treatment and/or training protocol (Week 5) 6 mice per group were subjected to the running test. Three mice in each group were not subjected to treadmill test to confirm that changes observed in the skeletal muscle were not due to the acute run, but related to the exercise training. It should be noted that the above interventions do not affect body weight and food intake in mice (data not shown).
In another study, male C57B/6J mice (8 wks old) were treated with GW1516 (5 mg/kg/day, oral gavage), AICAR (250 mg/kg/day, i.p.) or the combination of the two drugs for 6 days for gene expression analysis. Additionally, C57B/6J mice (8 wks old) were also treated with AICAR (500mg/kg/day, i.p.) for 4 weeks for treadmill running tests.
