Dietary Induced Obese Animals
Dietary-induced obese (DIO) rats and mice are well-established animal models of obesity. The obesity is induced by exposure to a single source high-fat diet (male mice) or a simplified cafeteria diet (female rats) for 3 to 4 months to mirror a typical calorie-dense Western diet. In both cases, once obesity has been induced, the animals are more or less weight-stable, display marked visceral adiposity (30-35% fat), high levels of leptin, moderate insulin resistance (rather than overt diabetes) and mild lipid abnormalities. A further similarity is that dietary-induced obesity in animals and man is polygenic in nature ie the susceptibility for weight gain is due to a number of different genes. In these respects the animals display similar symptoms to those observed in common human obesity (face validity) and the factors contributing to the initiation and maintenance of obesity are similar in animals and man (construct validity).
A variety of centrally- and peripherally-acting compounds including sibutramine, rimonabant and orlistat have now been tested in our DIO mice and rats. DIO mice can be produced using diet supplying 45% or 60% calories as fat. The DIO rat model was used in the global registration of sibutramine and has been found to have excellent predictive validity with a high degree of correlation between the magnitude of weight loss produced by antiobesity drugs and drug candidates in clinical trials and in dietary-induced obese female rats.
A number of optional additional studies can be used to investigate whether novel drugs selectively reduce adiposity or improve glycaemic control and plasma lipid profiles in the dietary-induced obese animals. These are critical clinical outcomes when evaluating the benefits of new drugs for weight management.
