An Overview of Murine High Fat Diet as a Model for Type 2 Diabetes Mellitus

Abstract

Type 2 diabetes mellitus (T2DM) is a worldwide epidemic, which by all predictions will only increase. To help in combating the devastating array of phenotypes associated with T2DM a highly reproducible and human disease-similar mouse model is required for researchers. The current options are genetic manipulations to cause T2DM symptoms or diet induced obesity and T2DM symptoms. These methods to model human T2DM have their benefits and their detractions. As far as modeling the majority of T2DM cases, HFD establishes the proper etiological, pathological, and treatment options. A limitation of HFD is that it requires months of feeding to achieve the full spectrum of T2DM symptoms and no standard protocol has been established. This paper will attempt to rectify the last limitation and argue for a standard group of HFD protocols and standard analysis procedures.

Comorbid diabetes results in immune dysregulation and enhanced disease severity following MERS-CoV infection

“…Of note, the IC 50 for a wide range of gliptins is similar between mice and humans when enzymatic inhibition is tested in vitro (46). We found that DPP4 H/M mice developed T2D similarly to wild-type C57BL/6 mice when fed an HFD (40,47). The species cross-reactivity of gliptins as well as other drugs used to treat T2D, including metformin and sulfonylureas, will allow us to study the effects of anti-T2D drugs on MERS-CoV pathogenesis.…”

“…We previously characterized a mouse model that showed significant pathology following MERS-CoV infection when exons 2-25 of mouse DPP4 were replaced with human DPP4 sequence (DPP4 H/H ) in mice on a C57BL/6 background (34,35). Importantly, C57BL/6 mice are susceptible to the development of obesity and T2D after being fed an HFD for an extended period (40,41). Although we have not observed any physiological or immunological differences between DPP4 H/H and wild-type mice, we chose to use mice that were heterozygotes for the human DPP4 allele (DPP4 H/M ) to avoid any unknown species-specific complications.…”

“…Mice were then evaluated for the development of metabolic disease. Studies focused on animal models for obesity and diabetes have found sex-specific differences in C57BL/6 mice in which males were more susceptible to both obesity and T2D (40). For these reasons, experimental groups were stratified by diet and by sex.…”

Mitochondrial Pyruvate Carriers are not Required for Adipogenesis but are Regulated by High‐Fat Feeding in Brown Adipose Tissue

“…This literature suggests that the decreased MPC expression correlated with decreased diet‐induced thermogenesis that occurs with prolonged high‐fat feeding. Also, the sex‐specific regulation of MPCs (Figure ) is likely attributed to sex‐specific metabolic responses to high‐fat feeding in C57BL/6J mice . Unlike male mice, previous studies have shown that female mice were more metabolically healthy, had reduced inflammation, and were more insulin sensitive despite having obesity while on an HFD .…”

The soluble guanylate cyclase stimulator IW‐1973 prevents inflammation and fibrosis in experimental non‐alcoholic steatohepatitis

“…In line with the anti‐steatotic actions seen in our study, cardiomyocytes overexpressing a constitutively active sGC showed better fatty acid trafficking and reduced TAG accumulation (Khairallah et al ., ). An interesting feature of the HFD model is that it provides the optimal setting to investigate the influence of extrahepatic factors, mainly those derived from WAT, on the progression of hepatic steatosis (Heydemann, ). Indeed, our study demonstrated that the beneficial effects of the sGC stimulator IW‐1973 were not only limited to the liver but also extended into the WAT depot.…”