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.

Hypothalamic inflammation in metabolic disorders and aging

“…Although it is too early to conclusively resolve these discrepancies, it is possible to speculate that HFD in animal models does not fully mimic the human T2DM pathogenesis. This condition is a significant obstacle hampering translational studies on brain dysfunction in T2DM patients [266]. Amid these findings, understanding microglial activity in hypothalamic inflammation and its impact on metabolic diseases and aging will be beneficial in microglial research for designing successful treatment techniques.…”

Tannins in the Treatment of Diabetic Neuropathic Pain: Research Progress and Future Challenges

“…Insulin resistance, one of the critical characteristics of type 2 diabetes, is triggered by a high carbohydrate and fat diet. Low-dose STZ injections can cause a modest decrease in insulin production, similar to the latter stages of type 2 diabetes (Stott and Marino, 2020). However, the benefit of phytochemical tannin treatment on hyperglycemia and body weight in the DNP animal model is equivocal, with findings varying depending on the rat species, types of diabetes, DNP induction techniques, and substances delivery procedures.…”

“…Treatment with phytochemical tannins has also been shown to help with DNP hyperalgesia and allodynia symptoms. Its anti-inflammatory, antioxidant, and antihyperalgesic properties are thought to be the mechanism for decreasing these symptoms ( Stott and Marino, 2020 ). According to Abo-Salem et al (2020) , treatment with EGCG alleviated hyperalgesia responses indicated by a hot plate, tail immersion, formalin, and carrageenan-induced oedema tests in STZ-induced diabetic rats.…”

Mammalian hibernation: a unique model for medical research

“…Insulin resistance and hyperinsulinemia were reported to facilitate fat storing during the fattening period and be reversible during hibernation period [38]. The rapid and dramatic increase of body fat mass generally lead to the metabolic diseases, such as diabetes mellitus and atherosclerosis in laboratory rodents [39]; however, no atherosclerotic changes were found despite highly elevated plasma lipids in bear and ground squirrels [40][41]. Recently, the candidate noncoding cis elements that regulates hibernator fattening were identified by comparative phylogenomics [42].…”