Considerations to maximize fat mass gain in a mouse model of diet-induced weight gain

Abstract

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

Murine models provide insight to the development of non-alcoholic fatty liver disease

“…Due to the association between adipose tissue inflammation, insulin resistance and steatosis, diets high in saturated fat are often used to model obesity, glucose intolerance and NAFLD in mice (56) . Due to the association between adipose tissue inflammation, insulin resistance and steatosis, diets high in saturated fat are often used to model obesity, glucose intolerance and NAFLD in mice (56) .…”

“…Due to the association between adipose tissue inflammation, insulin resistance and steatosis, diets high in saturated fat are often used to model obesity, glucose intolerance and NAFLD in mice (56) . Comparison of diets ranging in fat from 30 to 60 % demonstrated that a diet containing >45 % of energy from fat results in the greatest weight gain after 18 weeks of treatment in CD-1 mice (56) . Comparison of diets ranging in fat from 30 to 60 % demonstrated that a diet containing >45 % of energy from fat results in the greatest weight gain after 18 weeks of treatment in CD-1 mice (56) .…”

“…When choosing an animal model to study NAFLD there are a number of characteristics that should be considered. Due to the association between adipose tissue inflammation, insulin resistance and steatosis, diets high in saturated fat are often used to model obesity, glucose intolerance and NAFLD in mice ( 56 ) . Depending on the primary aim of the study it is key to identify the differences in dietary models as HFD alone have been shown to lead to alterations in weight gain and insulin sensitivity compared with high-sucrose and high-fat diets, and high-sucrose diets ( 57 , 58 ) .…”

“…Depending on the primary aim of the study it is key to identify the differences in dietary models as HFD alone have been shown to lead to alterations in weight gain and insulin sensitivity compared with high-sucrose and high-fat diets, and high-sucrose diets ( 57 , 58 ) . Comparison of diets ranging in fat from 30 to 60 % demonstrated that a diet containing >45 % of energy from fat results in the greatest weight gain after 18 weeks of treatment in CD-1 mice ( 56 ) . Extrapolation of findings from HFD-fed mice must be used with caution as certain obesity-related diseases are more representative of the human condition than others ( 59 ) .…”

On the importance of food

“…In this issue several articles are published with relevance to diets and animal experimentation. [1][2][3][4][5][6] One needs to realize that feeding laboratory animals has become important and questions arise on the content of chow pellets, the consistency or variations in food pellet formulae according to specific diets, or research objectives. It has long been known that diets may affect health and longevity, or influence a variety of diseases, 7,8 including many types of cancer, cardiovascular diseases, obesity, behavioral or age-related changes and cognition.…”