Rat models of diet-induced obesity and metabolic dysregulation: Current trends, shortcomings and considerations for future research

Rat diet-induced obesity and metabolic dysregulation (DIO/DIMD) is widely used as a pre-clinical model for human obesity and for testing weight-loss interventions. The aim of this review was to utilise a systematic literature survey of rat DIO/DIMD studies as a tool to document trends around study design and metabolic outcomes of these studies, and to consider ways in which the design of these studies may be improved to enhance the relevance thereof for human obesity research. In total, 110 comparisons between control and obesogenic dietary groups were included in the survey. Young male rats were found to be the model of choice, but fewer than 50% of studies provided comprehensive information about diet composition and energy intake. In addition, it was found that the majority of expected DIO/DIMD responses (hyperglycemia, hyperinsulinemia, dyslipidemia, hypoadiponectinemia) occurred at < 80% frequency, drawing into question the concept of a "typical" or "appropriate" response. We discuss the impact of differences in diet composition and energy intake on metabolic outcomes against the context of large heterogeneity of obesogenic diets employed in rat DIO/DIMD studies, and provide recommendations for the improvement of reporting standards around diet composition and dietary intake. In addition, we highlight the lack of data from female and older rats and describe considerations around the inclusion of sex and age as a variable in rat DIO/DIMD studies, aiming towards improving the applicability of these studies as a model of human obesity, which is most prevalent in women and older individuals.