Determining the Influence of a Novel Rodent Diet on Body Weight Gain and Renal Health in Male Mice from 2 Different Strains
Diet has an established relationship with health in humans; yet it is poorly represented or significantly oversimplified in most preclinical animal studies. Based on recent data, the “typical” American adult consumes a diet that is inadequate in several nutrients and high in salt and energy yielding compounds (particularly simple sugars). However, rodents diets used to model the nutritional composition of developed (or “Western”) societies do not embody these same inadequacies. Interestingly, many of the nutritional inadequacies noted in developed countries have been independently shown to negatively affect renal health in animal models. However, to our knowledge no animal studies have adequately determined the physiological consequences of consuming a diet modeling the complex nutritional inadequacies of Americans. Based on this information, we hypothesized that mice consuming an “Americanized diet” (AD) would have greater weight gain and evidence of renal injury as compared to mice fed chow. 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 (3-week old) male 129 Svlm/J (129, n=10) and C57Bl/6J mice (B6, n=10) were obtained from Jackson Laboratory and given 1 week to acclimate to solid diet. Mice were then assigned (n=5 per strain) to remain on a commercially available chow diet or our novel AD formulated to have similar nutritional inadequacies as reported by recent NHANES anlyses. Mice were given ad libitum access to their respective diets for 6 weeks and 24-hour dietary intake and body weights were recorded throughout the study. At the end of the 6-week feeding study, mice were individually housed in metabolic cages to collect urine for determination of albuminuria by ELISA. Renal blood flow was estimated using contrast-enhanced ultrasonography. All statistical analyses were performed using general linear models in SPSS. The B6 mice had higher average 24-hour caloric intake and resulted in a significant increase in body weight in the B6 mice (P=0.01), with the B6 mice consuming the AD having the highest food intake and overall body weight. Strain and diet both significantly influenced urinary output regardless of water intake (covariate), with higher (P=0.03) urinary output in the 129 strain (0.9±0.1 vs 0.4± 0.1 mL urine/day, 129 and C57Bl/6 respectively) and in mice consuming the AD diet (0.8±0.1 vs 0.5±1 mL urine/day). Regardless of strain, all mice consuming the AD tended (P=0.06) to have a greater 24 hour albumin excretion (26.7±4 μg) as compared to mice consuming chow (14.7±4 μg). Strain also significantly influenced estimated renal blood flow regardless of diet, with the B6 mice having a greater (P=0.02) estimated renal blood flow as compared to the 129 strain. Taken together, our data strongly suggest that a rodent diet formulated to match the nutritional quality of a “typical” American significantly influences renal health, particularly albuminuria and daily urinary volume. These data also highlight a strain difference in regards to renal outcomes alone or in combination with diet. Further studies are needed to elucidate the physiological mechanisms dictating these differences and provide insight into the nutrients involved in initiating renal dysfunction.
Brittney Browning, Hannah Ter Harr, Barbara Lutz, and Joseph Christopher Gigliotti, Determining the Influence of a Novel Rodent Diet on Body Weight Gain and Renal Health in Male Mice from 2 Different Strains, The FASEB Journal, Volume 32, Supplemental Issue 1, April 2018, https://www.fasebj.org/doi/abs/10.1096/fasebj.2018.32.1_supplement.851.5