Results and Discussion
C3H/HeJ mice fed a high fat diet develop diet-induced obesity (DIO) similar to C57BL/6N mice. Based on previous literature and preliminary studies, we identified C57BL/6N and C3H/HeJ mice as resistant and susceptible models, respectively, to mouse hepatitis virus 1 (MHV-1) 35,36. C57BL/6N mice are an established model of diet-induced obesity (DIO)37 and experience mild disease following MHV-1 infection38. Numerous studies have demonstrated that C3H/HeJ mice—which experience severe disease following MHV-1 exposure—exhibit resistance to DIO39-41. Conversely, other research has indicated that they exhibit dietary responses similar to C57BL/6N mice42. Therefore, to establish a model of obesity for studying its impact on MHV-1 infection, we used both mouse strains. C57BL/6N and C3H/HeJ mice fed a high-fat diet (HFD) had significantly higher weights compared to those on a low-fat diet (LFD) from 2-weeks-post-diet-initiation (Fig.1A & B, **p=0.0010 and **p=0.0030 respectively), which gradually became more significant by 18 weeks (Fig.1A & B, ****p<0.0001). Non-fasting glucose levels at 16-weeks-post-diet-initiation were significantly higher in obese mice compared to their lean counterparts in both, C57BL/6N and C3H/HeJ mice (Fig.1C & D, ***p<0.0001 and ***p=0.0005). This 18-week diet regimen produced C57BL/6N and C3H/HeJ mice that mirrored obesity and hyperglycemia in humans and, therefore, were appropriate to study the effect of obesity on coronavirus infection.