Many diabetes and obesity research studies rely on diet induced obesity (DIO) models, but there are many options and considerations for maximizing the effectiveness of your study. Two Inotiv scientists recently shared their insights on how to select and develop the optimal DIO model that meets your research needs.1. Evaluate your study design and endpoints
Before comparing diet induced obesity models, it is important to consider the hypothesis of your study, its design and the endpoints of the study.
“Are you studying diabetes in addition to obesity? Is your compound examining weight loss or the impedance of weight gain? These are important factors to communicate to your animal model vendor,” explained Mandy Horn, Scientist, Veterinary Science, Research & Support at Inotiv. “Your vendor can help evaluate your study, learn when you want to induce DIO during the study, and use this information to determine which particular stock, strain or substrain would work best, as well as the help you determine how the sex of the mice may influence phenotype.”
2. Research historical control data and peer-reviewed publications
Published references can provide a wealth of information for spontaneous and diet induced metabolic models. Depending on the stock, strain and sex, models have varying responses to high fat diets. Inotiv has published C57BL/6Hsd “Black 6” publications related to DIO and can provide data on RccHan:WIST female DIO.
“We’ve done in-house studies to optimize development of gonadal intact female Wistar Han rats to compare a variety of high fat diets and determine if they could create a reliable obesity model,” said Sheryl Wildt, Global Manager of Genetic Quality and Breeding. “We found that Wistar Han® female rats can be a useful for testing new anti-obesity compounds to determine if they can prevent or reduce obesity without making a previously healthy model develop unhealthy side effects.”
“Historical control data is helpful to make informed decision about your model,” added Mandy. “We recommend that you evaluate the model’s typical weight gain over time as some models may slow down or plateau over time whereas other models may continue to gain weight well into 20-24 weeks of age.”
3. Understand the differences with diet
Your animal model vendor will want to discuss the options for your models’ diet as it impacts the phenotype of the model. Diet vendors, including Teklad, can make any customized high-fat diet to meet the needs of your study. These vendors can alter the fat source or even adjust the ratio of omega-3 to omega-6 fatty acids or the ratio of long-chain to medium-chain fatty acids.
“There are many considerations, such as a plant-based fat, such as coconut oil, or animal-based fat, such as lard, for your fat source,” explained Mandy. “Diets can also have increased sugars, although with a higher fat content at 55-60%, the carbohydrates are relatively low when compared to other obesity inducing diets with 40-45% of the calories from fat, often referred to as the ‘Western Diet.’”
4. Setting up your study for success
Once you have selected the ideal model for your study, you need to consider the age at which to start your models’ diet, based on the goals of your research. Typically, the high fat diet begins in mouse models around three to six weeks of age, depending on your study design and whether you are trying to treat or prevent obesity.
In terms of housing your mice, housing density can affect overall weight gain. Co-housed mice can gain weight faster than single-housed mice, but this difference may vary among models. For enrichment, nesting materials, shredded paper and wood bedding are recommended for the DIO mice. Mice and rats will sometimes eat corncob bedding, which can have an effect on metabolism, adding a confounder to your study. Bedding may also need to be changed more frequently if your model becomes diabetic, due to increased urine output.
“Weight increases in your DIO group may be noticed after one to two weeks of feeding as compared with the control, depending on the model. Some models may not show a difference in body weight from controls for six to eight weeks.” said Sheryl. “Other more severe phenotypes may take up to 10-12 weeks to appear. Depending on the model, weight gain can continue past 20 weeks of age, which researchers should take into account for their study’s endpoints.”
5. Outsourcing your DIO model development
One alternative to creating your own DIO model is outsourcing the work to a proven supplier. Envigo can manage the models and develop them to reach a certain weight or phenotype.
“The typical timeline requires 6-8 weeks; other models may require more time,” explained Mandy. “We can use our own Teklad Diets or work with the customer’s specified diet. We manage the inventory and monitor the weight gain to deliver study-ready DIO models. The process is completely customizable to meet the needs of the customer’s study.”
Whether developing your own DIO model or outsourcing, learn more about diet induced obesity at Inotiv.