Determining the Effect of Diet on Renal Health and Function in 2 Strains of Mice

Diet remains a key contributor to health and disease worldwide. However, diet is routinely overlooked or oversimplified in basic biomedical research. Most preclinical animal studies are performed in young mice fed a grain-based chow diet that is supplemented to ensure adequate nutrition. Those studies that consider diet typically use commercially available formulas that significantly oversimplify the dietary patterns of “Western” societies. We have developed a novel “Americanized” rodent diet (AD) that is a more holistic representation of American dietary quality and was further adjusted based on mouse requirements. Our preliminary studies found mice consuming the AD differed in measures of renal function as compared to mice fed chow in two different strains. Therefore, in the current study we set out to determine if the AD deferentially influences renal health as compared to a commercially available “Western” diet (WD) in 2 strains of mice. 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 or 129SvEv strains were purchased from Taconic and acclimated to the new environment and chow diet for 1-week. After one week, mice were given ad libitum access to chow (18% protein), our AD, or WD for 8 weeks (n=6). The AD consists of a modified chow pellet and synthetic pellet formulated to match the reported 50th percentile of American intake for several nutrients. After 8 weeks, mice were placed in metabolic cages to quantify water intake and urinary excretion. Renal blood flow (RBF) was determined in these mice using contrast-enhanced ultrasonography and blood pressure using a non-invasive tail-cuff method. Mice were then euthanized and kidney samples collected for histological assessment. All statistical analyses were performed using general linear models in SPSS, with “Diet” and “Strain” as the independent variables. Diet significantly influenced water intake (but not strain), with mice fed chow consuming 4–5mL of water per day, as compared to ~3mL/day observed in mice fed AD or WD (P\u3c0.001). After correcting for differences in water intake (water intake as a covariate), strain had a significant influence on urinary output, with the C57Bl/6 mice having a greater 24 hour urinary volume as compared to the 129 strain (P=0.02). Furthermore, mice fed the AD had significantly lower estimated RBF as compared to mice fed chow (P=0.03), with a marked reduction in inner medullary blood flow (P\u3c0.02) as compared to mice fed chow or the WD. Strain also tended to influence the effect of diet on systolic blood pressure (strain*diet P=0.07), with mice of the 129 strain fed the AD having the lowest blood pressure that was significantly different from mice fed chow (P=0.02). Taken together, our results suggest that diet (particularly the AD) significantly influences renal function and this effect is further influenced by mouse strain. These results suggest that preclinical animal studies should consider diet in a holistic manner and more research is needed to delineate the physiological mechanisms by which the AD directly impacts renal function