Obesity

Obesity is defined as being more than 20% (men) or 25% (women) overweight. Obesity is increasing rapidly throughout the developed world, and has increased from 13% to 31% in the US in the past 30 years. In the US, it is estimated that 63.6 million adults or 31.4% of the population are obese, of whom a significant percentage are morbidly obese. Obesity dramatically increases the chances of developing Type II diabetes, cardiovascular disease and certain types of cancer. The primary causes of obesity are excessive calorie intake and lack of physical activity.

Genetic Obesity

There are numerous genetic models of obesity in both rats and mice, including the Zucker and ZDF rats and ob/ob and db/db mice, in which obesity develops spontaneously. Animals are weighed daily to track weight change and their blood glucose levels can also be monitored. After animals are sacrificed, serum chemistry can be performed and samples of skin with adjacent subcutaneous fat can be harvested.

Study Design Table

Model Description Duration Endpoints
Genetic Obesity Zucker and ZDF rats, ob/ob and db/db mice 28-56 days Weight, Glucose levels, Terminal serum chemistry, Tissue sample

 

Diet-Induced Obesity

As excessive caloric intake with too little exercise is a primary cause of obesity our model of diet-induced obesity in mice and rats involves a high-fat, high-carbohydrate diet and is translatable to the human population. Additionally, this diet can be fed to animals with any genetic background. Animals are weighed daily to track weight change and their blood glucose levels can also be monitored. Dual-energy x-ray absorptiometry (DEXA) measurements can be taken to assess changes in bone and tissue composition. After animals are sacrificed, serum chemistry can be performed and samples of skin with adjacent subcutaneous fat can be harvested.

Study Design Table

Model Description Duration Endpoints
Diet-induced obesity Animals placed on high-fat, high-carb diet 28-56 days Weight, Glucose levels, DEXA analysis, Terminal serum chemistry, Tissue sample

 

Accumulating evidence suggests that foods’ nutritional value is partly influenced by the gut microbiome. Moreover, though the worldwide increase in obesity is certainly associated with increased caloric intake, the microbiome has also been demonstrated to play a role in obesity (Kau, et al., 2011). For example, cohort twin studies have demonstrated that the phylogenetic composition of the fecal microbiota is different in obese versus lean twins (Turnbaugh, et al., 2009). The potential effects of microbiome modulation in the diet-induced obesity model are thus of scientific interest. We therefore sought to determine the effects of microbiome modulation on body weight, blood glucose, and bone/tissue composition using the diet-induced obesity model.

Briefly, C57Bl/6NTac mice were pre-treated with antibiotic cocktail (Ampicillin, Clindamycin, Metronidazole, and Vancomycin) or vehicle, followed by treatment with a murine fecal microbial transplant or vehicle. Animals were maintained on standard chow for three weeks, and were weighed daily. Baseline pre- and post- prandial blood glucose and bone/tissue DEXA measurements were taken. Animals within each treatment group were then randomized by weight into sub-groups, and sub-group diets were switched from standard chow to either high-fat (HF) or control (cntrl) diets. Body weight was observed for an additional six weeks, after which time pre- and post- prandial blood glucose and bone/tissue DEXA measurements were repeated. 

(A) Dual-energy x-ray absorptiometry (DEXA) PIXImus 2. (B) Representative DEXA image.
Percent Body Weight Change, Days 0-21
Percent Body Weight Change, Days 22-63
Pre- and Post- Prandial Blood Glucose: (A) Days 20-21 and (B) 62-63
DEXA Bone Measurements: Day 21. (A) Bone Mineral Density, (B) Bone Mineral Content, (C) Bone Area.
DEXA Tissue Measurements: Day 21. (A) Total Lean Tissue Mass, (B) Total Fat Mass, (C) Total Percent Body Fat.
DEXA Bone Measurements: Day 63. (A) Bone Mineral Density, (B) Bone Mineral Content, (C) Bone Area.
DEXA Tissue Measurements: Day 63. (A) Total Lean Tissue Mass, (B) Total Fat Mass, (C) Total Percent Body Fat.
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