Determining the Effect of Diet on Weight Gain and Metabolic Dysfunction in 2 Strains of Mice
Medicine and Health Sciences
Diet has a significant impact on human health, yet it is poorly represented or significantly oversimplified in most preclinical animal studies. A majority of animals used in preclinical studies are fed grain-based chow pellets that are supplemented to exceed nutritional requirements. “Disease-inducing” or “Western” diets (WD) exist; however, they focus solely on the energy and cholesterol content and do not consider the effect of diet in a holistic manner. Previously we found mice consuming a novel “Americanized” diet (AD) had greater weight gain as compared to mice fed a chow diet in a strain dependent manner. In the present study, we set out to compare our AD to a commercially available WD in regard to severity of obesity and metabolic dysfunction in two different mouse strains. All experiments were performed in accordance with protocols approved by the Liberty University IACUC and conform to the FASEB Statement of Principles for the use of animals in research and education. 3-week old male mice of the C57Bl/6 and 129SvEv strains were purchased from Taconic and allowed to acclimate to the new environment and chow diet for one week. After acclimation, mice were given ad libitum access to chow (18% protein), the AD, or the WD (n=6) for 8 weeks. The AD consists of a modified chow pellet and synthetic pellet formulated to match the reported 50th percentile of American daily intake for several nutrients. Body weight and diet intake were recorded and animals were then euthanized and blood, liver, and adipose tissues were collected. All statistical analyses were performed using general linear models in SPSS, with “Diet” and “Strain” as the independent variables. Mice consuming the WD routinely displayed signs of distress (pyloerectus), which was less frequently observed in mice fed the AD and even less so in mice fed chow. Strain appeared to significantly influence the intake of energy-dense diets, with mice of the 129 strain consuming around 1 gram less of the WD per day when compared to the C57Bl/6 strain. This effect was also observed in mice consuming the AD, with the 129 strain consuming >0.5 gram less of the energy-dense synthetic pellet as compared to mice of the C57Bl/6 strain. These intake data likely explain the significant effect of diet (P<0.001), strain (P<0.001), and diet*strain interaction (P=0.002) on weight gain, with the C57Bl/6 mice and mice fed WD having the greatest weight gain, adipose tissue mass, and degree of hepatic steatosis. Diet was primarily responsible for changes in circulating HDL (P<0.001) and TRG (P=0.02), with WD and AD having similarly higher values than mice fed chow. Interestingly, strain significantly influenced the effect of diet on circulating glucose, with the 129 mice having lower average values as compared to C57Bl/6 mice (diet*strain P=0.001). Taken together, these data support our previous findings that dietary intake differs between mouse strains and subsequent measures of metabolic dysfunction. Future studies will determine how the expression of key metabolic enzymes differs between these strains and whether the expression profile is further influenced by diet.
Kristin Wiley, Daniel Quan, Juhie Patel, Christian Rose, Riley Lutz, and Joseph C. Gigliotti, Determining the Effect of Diet on Weight Gain and Metabolic Dysfunction in 2 Strains of Mice, The FASEB Journal, Volume 33, Supplemental Issue 1, April 2019, https://www.fasebj.org/doi/abs/10.1096/fasebj.2019.33.1_supplement.754.4