ICEMED Focus Group "DIO mouse models"
The prevalence of obesity has been increasing world-wide over the past decades. Massive fat accumulation, particularly in the visceral adipose depot, deregulates lipid- and glucose metabolism, giving rise to obesity-associated co-morbidities, such as diabetes and cardiovascular diseases. In order to examine the etiology of obesity in vivo, animal models have become invaluable.
Over the years, various mouse models and knock-out strains have been made available to study the genetic factors affecting body weight regulation and energy metabolism. In addition, different diet-induced obesity (DIO) animal models have been generated to mimic the progression and outcome of obesity. Thereby, DIO mice are considered to be more representative of the human pathogenesis, and thus are often preferred over genetic models (Fig.1).
The DIO phenotype is not only dependent on the genetic background and gender of the mice, but is also affected by the specific environment of the animal facility. Yet, the dietary composition and caloric value of the (high-fat) diet are considered the most relevant factors regarding the individual progression of DIO (Fig.2). However, little is known about the interaction between the maintenance environment and the individual susceptibility towards obesity.
Reviewing 2013’s high-impact journal publications for strategies used for DIO in mice, a great heterogeneity was found regarding the experimental procedures. This was associated with substantial variability in the published DIO phenotypes, thus potentially affecting the repeatability of mouse experiments in different laboratories.
The goal of this PhD project is to characterize the development of DIO in mice and to create a guideline on how to optimally establish DIO in male and female mice under a set of standard conditions.
As a first step, two of the most commonly fed high-fat diets will be used for a DIO experiment under standard maintenance conditions. Thereby, the progression of the disease will be characterized comparing male and female of the most frequently used mouse strain.
As a second step, a multi-center based mouse DIO experiment will be set up in laboratories of the ICEMED partners in Germany, comparing the progression of the disease in different laboratory environments.
Based on these experiments, a reference guide for the development of DIO in mice under standardized conditions will be published.
Fig. 1 Mice phenotypes under diet induced obesity (DIO).
Fig. 2 Factors influencing diet induced obesity (DIO) experiments.