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Abstract: TH-PO539

Do You Know What Your Experimental Animals Eat?

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Biruete, Annabel, Indiana University School of Medicine, Muncie, Indiana, United States
  • Srinivasan, Shruthi, Indiana University School of Medicine, Muncie, Indiana, United States
  • O'Neill, Kalisha, Indiana University School of Medicine, Muncie, Indiana, United States
  • Vorland, Colby, Indiana University, Bloomington, Indiana, United States
  • Hill Gallant, Kathleen M., Purdue University, West Lafayette, Indiana, United States
  • Cai, Weijing, Mount Sinai Medical center, New York, Nevada, United States
  • Uribarri, Jaime, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Johnston, Nancy, Indiana University School of Medicine, Muncie, Indiana, United States
  • Allen, Matthew R., Indiana University School of Medicine, Muncie, Indiana, United States
  • Chen, Neal X., Indiana University School of Medicine, Muncie, Indiana, United States
  • Moe, Sharon M., Indiana University School of Medicine, Muncie, Indiana, United States
Background

Autoclaved diet use has been increasing in research animal facilities due to its ability to reduce infection. The high heat generated through autoclaving could have various effects on a diet. Our goal was to determine how autoclaved-induced increases in dietary advanced glycation end products (AGE) affect properties in a model of chronic kidney disease-mineral and bone disorder (CKD-MBD).

Methods

Cy/+ (CKD) rats and normal (NL) littermates were assigned to 1 of 3 diets: autoclaved 0.7% phosphorus grain-based diet for 28 wks (AGEs), autoclaved diet for 17wks followed by non-autoclaved 0.7% bioavailable phosphorus casein-based until 28 wks (AGEs + Casein), or a non-autoclaved diet for 17wks followed by a non-autoclaved casein-based diet (non-AGEs+Casein) until 28 wks. We examined kidney function, plasma biochemistries, and intestinal gene expression (phosphate transporters, the receptor for AGE (RAGE), and NADPH-oxidases). We assessed the effects of disease (CKD vs NL), diet, and the interaction by two-way ANOVA.

Results

Autoclaved diet contained 3.5-fold more of the AGE carboxymethyllysine and 2.5-fold more methylglyoxal than the non-autoclaved diet. There was a disease-by-diet interaction on the plasma DNA oxidation marker 8-OHdG, driven by differences between the NL and CKD rats fed the AGEs and AGEs + Casein diets. AGEs diet led to increased progression of CKD that was further augmented by the casein diet (Pinteraction=0.03). There was a disease-by-diet interaction on phosphorus, PTH, and FGF23 driven by the higher values in the CKD rats fed the AGEs + casein diet (P interaction<0.05 for all). At the intestinal level, NaPi2b was 2-fold higher in the rats fed the non-AGEs + casein diet (Pdiet<0.0001). Intestinal RAGE was 2- to 4-fold higher in the rats fed the AGEs and AGEs + casein diets (Pdiet<0.0001). This was mimicked by a higher expression of DUOX2 (Pdiet= 0.0019).

Conclusion

Autoclaved diet contains higher levels of AGE and leads to increased systemic oxidative stress and more rapid progression of CKD-MBD phenotype if combined with a bioavailable phosphorus diet. Eating an autoclaved diet also altered intestinal transporters regulating AGE, NADPH-oxidases, and phosphate. These studies highlight the critical importance of dietary aspects, including autoclaving, in the study of CKD-MBD.

Funding

  • NIDDK Support