Determining the Influence of a Novel Americanized Rodent Diet on Renal Health in Wild-Type Mice Administered Angiotensin II
Medicine and Health Sciences
Diet has an established relationship with morbidity and mortality worldwide. While poor diet is primarily associated with cardiovascular disease, there is evidence that poor diet has a direct negative influence on renal health that can also contribute to deteriorating cardiovascular health. However, due to the lack of a well-designed disease inducing rodent diet, the physiological link between diet and the cardiovascular and renal systems remain unclear. We have developed a novel Americanized diet (AD) that is based on the nutritional intake of Americans and includes modifications to several nutrients while also accounting for the difference in human and mouse nutritional requirements. We hypothesized that mice consuming the AD will have greater weight gain and exacerbated renal injury, as compared to mice fed standard chow, in response to low-dose angiotensin II (AngII) administration. All animal experiments were performed following animal protocols approved by the Liberty University IACUC and conforms to the FASEB Statement of Principles for the use of animals in research and education. Weanling (3-week old) male C57Bl/6J mice were given ad libitum access to the AD (n=5) or standard laboratory chow (n=5) and ddH2O. 24-hour dietary intake and body weights were recorded weekly. After 5 weeks, a baseline urine sample was collected and a subcutaneous pump delivering AngII (250 ng/kg*min) was implanted in the rear flank. Systolic blood pressure was recorded daily during AngII infusion using a non-invasive tail-cuff volume pressure recording method. After 4 weeks of AngII infusion, another urine sample was collected and urinary albumin concentrations were quantified by ELISA. Prior to euthanasia, renal blood flow was estimated using contrast-enhanced ultrasonography. Body weight and blood pressure data were analyzed using generalized linear models (Two-Way Repeated Measures), while the remaining parameters were analyzed using a multivariate GLM procedure. All statistical analyses were performed using SPSS. Mice consuming the AD had greater weight gain (P<0.01) and urinary concentration of albumin (P=0.01) prior to AngII administration. Interestingly, the difference in weight was abolished upon initiation of AngII infusion despite a continued difference in estimated daily caloric intake. Albuminuria persisted in the mice consuming the AD after 4 weeks of AngII (38±10 vs 20±5 ug/24 hr, P=0.02), despite a lack of difference in blood pressure between the AD and chow fed mice (P=0.8). Estimated renal blood flow was also greater in mice fed the AD (P=0.02), and likely explains the tendency for higher 24 hour urine output (P=0.2) as compared to mice consuming chow and receiving AngII. In conclusion, mice consuming an AD had greater weight gain and renal damage (albuminuria) despite the absence of a change in systolic blood pressure. These data show that the nutritional quality of a “typical” American diet has direct negative impact on renal health in rodents and further studies are needed to further elucidate the consequences of these findings.
Alex Walker Johnson, Jacob Convissar, Jessica Joshua, Damir Pogarcic, and Joseph Christopher Gigliotti, Determining the Influence of a Novel Americanized Rodent Diet on Renal Health in Wild-Type Mice Administered Angiotensin II, The FASEB Journal, Volume 32, Supplemental Issue 1, April 2018, https://www.fasebj.org/doi/abs/10.1096/fasebj.2018.32.1_supplement.851.3