High Fat Rodent Models of Type 2 Diabetes: From Rodent to Human

Abstract

Poor dietary habits contribute to increased incidences of obesity and related co-morbidities, such as type 2 diabetes (T2D). The biological, genetic, and pathological implications of T2D, are commonly investigated using animal models induced by a dietary intervention. In spite of significant research contributions, animal models have limitations regarding the translation to human pathology, which leads to questioning their clinical relevance. Important considerations include diet-specific effects on whole organism energy balance and glucose and insulin homeostasis, as well as tissue-specific changes in insulin and glucose tolerance. This review will examine the T2D-like phenotype in rodents resulting from common diet-induced models and their relevance to the human disease state. Emphasis will be placed on the disparity in percentages and type of dietary fat, the duration of intervention, and whole organism and tissue-specific changes in rodents. An evaluation of these models will help to identify a diet-induced rodent model with the greatest clinical relevance to the human T2D pathology. We propose that a 45% high-fat diet composed of approximately one-third saturated fats and two-thirds unsaturated fats may provide a diet composition that aligns closely to average Western diet macronutrient composition, and induces metabolic alterations mirrored by clinical populations.

Keywords: high-fat diet; insulin resistance; metabolism; obesity; rodent models of type 2 diabetes; type 2 diabetes.

Figure 1

Rodent tissue responses to Western-like diet. A 45% HFD provides a progressive development of tissue and whole-body changes consistent with the T2D-like phenotype. Using higher fat percentages may create a greater magnitude of tissue dysfunction or accelerate the process, resulting in missed opportunity to study key aspects of disease progression. Detailed tissue responses could be found in Table 1 through Table 5. High-fat diet (HFD), Type 2 Diabetes (T2D), Triacylglycerol (TAG) and Diacylglycerol (DAG).