Determining the Effect of a Novel Disease-Inducing Rodent Diet on Outcomes of a Murine Model of Polymicrobial Sepsis
Sepsis affects more than a million Americans each year and is responsible for more deaths in the United States than prostate cancer, breast cancer, and AIDS combined. Obesity has been positively associated with the severity of sepsis amongst patients in the ICU, suggesting diet significantly influences the pathophysiology of disease. Animal studies support the interaction of diet with sepsis pathogenesis and severity; however the diets used have a drastically different nutrient profile as compared to the reported nutritional intake of Americans. Therefore, the goal of the current application was to determine how a novel rodent diet that adequately models the complex nutrient composition of Americans (Americanized diet - AD) influences the severity of sepsis in mice. All animal experiments were performed following animal protocols approved by the Liberty University IACUC and conform to the FASEB Statement of Principles for the use of animals in research and education. Weanling male C57Bl/6 mice were fed either chow (n=5) or the AD (n=5) ad libitum for 8 weeks with body weights and 24-hour dietary intake collected weekly. After 8-weeks, mice underwent cecal-ligation and puncture to induce polymicrobial peritonitis. 24 hours later blood was collected, animals were euthanized, and kidney and spleen tissues were collected. Circulating interleukin-6 (IL6) and blood urea nitrogen (BUN) concentrations were determined using commercially available assays. Kidney and splenic IL6, TNFα, and C3 gene expression were measured using RT-PCR and expression normalized to GAPDH using the delta-Ct method. All data were analyzed using general linear model analyses in SPSS. Mice consuming the AD tended (P=0.05) to have significantly greater body weights starting after 4 weeks of feeding as compared to mice consuming chow. Following CLP, systemic IL6 values were significantly greater (P=0.04) in mice fed the AD (80±22 μg/mL plasma) as compared to chow fed mice (18±10). There was also a numerical increase in BUN in the AD fed mice following CLP (120±22 mg/dL) as compared to mice fed chow (70±35); however this did not reach statistical significance (P=0.16). No difference was observed in TNFα or C3 mRNA expression in the kidney or spleen; however, there was a 4-fold increase in splenic (but not renal) IL6 mRNA expression in mice fed the AD as compared to mice fed chow (n=3). Taken together, these data highlight the significance of diet to the immunopathology of polymicrobial sepsis in mice and suggest that diet has a direct impact on IL-6 production in the spleen.
Jessica Joshua, Damir Pogarcic, Jacob Convissar, Alex Walker Johnson, and Joseph Christopher Gigliotti, Determining the Effect of a Novel Disease-Inducing Rodent Diet on Outcomes of a Murine Model of Polymicrobial Sepsis, The FASEB Journal, Volume 32, Supplemental Issue 1, April 2018, https://www.fasebj.org/doi/abs/10.1096/fasebj.2018.32.1_supplement.874.5