Mouse experimental models of diet-induced weight gain are commonly used as analogs to human obesity; however, a wide variety of feeding methods have been used and the most effective way to maximize weight gain is not known. Maximizing weight gain may allow for a reduction in the number of animals required for a given experiment. The purpose of this study was how to cause the greatest amount of weight gain in CD-1 mice by modifying the composition and source of their diet. To accomplish this goal, we completed two experiments: (1) Effect of dietary macronutrient fat intake (60% (HF60), 45% (HF45), 30% (HF30), or 13.5% (CON) fat diet for 18 weeks); and (2) Effect of 1:1 mixed HF60 and CON diets. Outcome measures included food intake, body mass, and body composition, which were measured bi-weekly and statistically analyzed using a repeated measures analysis of variance (RM-ANOVA). In Experiment 1, the greatest increase in body and fat mass was observed in HF60 (36%) and HF45 (29%) compared with HF30 and CON (P < 0.05). In Experiment 2, HF þ stock diet (SK) gained 25% more body mass and 70% more fat mass than HF (P < 0.05). Collectively, these findings suggest that using a high-fat based diet (>45% calories from fat), mixed with a stock diet, results in substantially more weight gain over a similar period, of time, which would allow an investigator to use $40% fewer animals in their experimental model.
Keywords mouse diet-induced weight gain, dietary fat, obesity, disease, mixed dietsIn the past decade, the prevalence of overweight/obesity has reached epidemic levels in many parts of the world, resulting in a rise in morbidity and premature mortality.1,2 Studying the longitudinal effects of dietinduced weight gain in humans is problematic due to ethical considerations. Thus, rodent weight gain models are an attractive analog for human obesity. One limitation of the current studies is that a wide variety of weight gain methodology has been used and it is not clear which method most effectively maximizes weight gain. [3][4][5][6][7][8][9] Through a series of investigations, our laboratory has sought to address this limitation in the current literature. We have previously demonstrated that mice that are group-housed (groups of five) and restricted from structured physical activity have greater weight gain than normal growth rates.10,11 Consistent with reports from other laboratories, we have also demonstrated that extremely high-fat diets (60% of calories from fat) result in excessive weight gain above normal growth.10 Neither our laboratory nor others have specifically compartmentalized weight gain into lean and