“…The tremendous genetic diversity of the CC population (Philip et al, 2011 ; Collaborative Cross Consortium, 2012 ; Srivastava et al, 2017 ; Shorter et al, 2019 ) facilitates the discernment between effects caused by diet from effects caused by genetic variation when measuring differences and changes in adiposity and other metabolic traits across multiple genetic “replicates” in each strain, thereby increasing power, reproducibility, and relevance to obesity in humans (Mathes et al, 2011 ). Following a 2-week acclimation period on standard synthetic diet (AIN-76A) to determine baseline phenotypes, mice between 8 and 11 weeks of age were randomized and put on experimental diets (high fat high sucrose or high protein) for 8 weeks, followed by analysis of body composition, metabolic rate, clinical blood chemistries, and circulating metabolites to assess the effect of diet on each trait since diets with higher protein, low glycemic index, and lower fat content may assist in maintaining weight loss compared to diets with higher carbohydrate content (Abete et al, 2010 ; Larsen et al, 2010 ; Hu et al, 2018 ; Myrmel et al, 2019 ; San-Cristobal et al, 2020 ). While both genetics and diet interact to influence adiposity and other phenotypes, health outcomes were more strongly impacted by genetic effects than diet.…”