Reduced activity without hyperphagia contributes to obesity in Tubby mutant mice

Abstract

The Tub gene was originally identified as a spontaneous mutation in C57Bl/6J mice, and associated with adult-onset obesity (Tub MUT mice). Although the original Tub MUT mouse was identified over 15 years ago, there have been few reports on the animal's food intake, body fat percentage or energy expenditure. In this study, we report food intake, body weight from 5-20 weeks, body fat, body temperature and three different measures of physical activity behavior. Tub MUT mice display reduced food intake, uncharacteristic of many obese mouse models, and reduced voluntary wheel running with normal home cage ambulatory behavior. We conclude that motivation for food and exercise is an underlying defect in TUB MUT mice.

Fig. 1

Food intake in WT, HET and TUB MUT mice. Food intake on standard rodent chow was measured for 20 weeks. Data is reported as the average daily intake ± SEM in grams for each genotype. ** P ≤ 0.01, *P ≤ 0.05 compared to WT.

Fig. 2

Body weight and percent fat in WT, HET and TUB MUT mice. A. Animals in the food intake study were used for the body weight analysis. Animals were weighed once weekly and the data is reported as the mean ± SEM in grams for each genotype. B. Mean percent carcass fat ± SEM for each genotype is reported for three age groups. Note that no HET animals were available for age group 2. **P ≤ 0.01, *P≤ 0.05.

Fig. 3

Body temperature in WT, HET and TUB MUT mice. Two age groups were used for each genotype. Body temperature is reported as mean °C ± SEM. **P ≤ 0.01.

Fig. 4

Activity, body weight and food intake for animals given assess to a voluntary wheel apparatus. A. Average total daily wheel revolutions ± SEM were reported for mice during the 5 week collecting period. B. Data from graph A was separate into lights on (6 AM – 5:50 PM) and lights off periods (6 PM – 5:50 AM) and reported as above. C. Body weight at each week of the activity testing is reported as mean grams ± SEM. **P ≤ 0.01.

Fig. 5

Circadian rhythm analysis in mice given access to a voluntary wheel apparatus. Average wheel rotations for 20 minute bins were averages for WT (A), HET (B) and TUB MUT (C) mice and plotted. Open bars on x-axis indicate light phase, while dark bars indicate dark phase. Standard error bars were left off this figure for simplicity, but are similar in magnitude to those in Figure 4.

Fig. 6

Rota-Rod and home cage ambulatory activity for WT, HET and TUB MUT mice. A. Animals were tested four times per day for four days on a Rota-Rod.rota-rod. The mean length of time performing the task (in seconds) ± SEM is reported. B. Total optical beam breaks ± SEM is reported for each genotype. ***P ≤ 0.001