Figure 3.

Influence of metformin and diet on body weight (BW) and serum hormones. Mice undergoing the carcinogenesis protocol described in Figure 2 were weighed every two weeks once groups were switched to either the 10 Kcal% fat (overweight control) or 60 Kcal% fat (Diet- induced obesity, DIO) diet. Serum was collected at the end of the 25-week promotion period (30 weeks total on the different diets). A, Treatment with metformin, rapamycin, or combinations of these compounds prior to TPA had no significant effect on BW gain in the overweight control groups. B, None of the treatment regimens affected weight gain in the obese groups compared to the TPA only group. The differences in average BW between the overweight control and DIO diet groups (including all treatment groups combined) were statistically significant (31.6 ± 0.86 vs. 45.2 ± 0.63, respectively, p<0.05, Mann-Whitney U-test). C, Fasting serum levels (mean ± SEM) of insulin, adiponectin, leptin, and IGF-1 in overweight or obese mice receiving TPA, metformin+TPA, rapamycin+TPA, or metformin+rapamycin+TPA at the doses indicated (n=4-7). * Indicates significantly different from the TPA only group, (p<0.05; Mann-Whitney U-test).