Figure 4: Effect of compound 1 on body weight, energy intake, body composition and insulin resistance in DIO mice
A: Body weight change in animals treated with vehicle, rimonabant or compound 1 over the study period. Average body weight of 8 mice per group is shown in grams. Means ± SD for each time point are shown. Statistical significance for each time point was analyzed by using repeated measures ANOVA procedure with post-hoc testing. Body weight change for compound 1 versus vehicle was significant from day 14 onwards (*P=0.02 and P=0.007 for days 14 and 35, respectively). Body weight change for rimonabant versus vehicle and compound was significant from day 4 onwards (*P=0.02 and P=0.0000004 for day 4 and day 35 respectively).
B: Food consumed by animals treated with vehicle, rimonabant or compound during study period. Food intake was measured daily for animals which were housed in groups of 4 per box. Average food consumption per box was calculated. The average daily food intake of 8 mice (2 boxes) per group is shown in grams. Means ± SD for each time point are shown. Statistical analysis was performed for each time point by using repeated measures ANOVA procedure with post-hoc testing. Difference between rimonabant and vehicle-treated mice was significant for days 1-8.
C: Data from B represented as bar graph. Average food intake for each group is averaged for days 1-8 and 9-33. *P=0.0004 for Rimonabant versus vehicle for days 1-8. Food intake differences for Rimonabant for days 9-33 were not significant. No significant difference between compound 1 and vehicle.
D: Energy intake expressed in terms of body weight: Average energy intake in kilocalories during 10 day period divided by body weight X 100. *P=0.03 for compound 1 versus vehicle for days 21-33.
E: Representative DEXA image of mice treated with either vehicle, rimonabant or compound 1. N=8 for each group.
F: Percent fat mass quantified by DEXA. Statistical analysis was performed using the two sample, paired t test. * P=0001 for rimonabant and P=0.002 for compound 1 compared to vehicle.
G: Lean (fat-free) mass (in grams) quantified by DEXA. Statistical analysis was performed using the two sample, paired t test. *P=0001 for rimonabant and P=0.02 for compound 1 compared to vehicle.
H: Effect of compound 1 on insulin resistance: Fasting glucose and insulin levels were determined at the end of the study. N=8 per group. HOMA-IR was calculated from fasting glucose and insulin values using the formula, (HOMA-IR): [fasting insulin (pM) X fasting glucose (mM)]/135. Statistical analysis was performed using the two sample, paired t test. * P=0.02 for compound 1 versus vehicle.