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Abstract: TH-PO939

Diet Significantly Influences the Induction of Endoplasmic Reticulum Stress (ERS) in the Kidneys of Male C57Bl/6 Mice

Session Information

Category: Health Maintenance, Nutrition, and Metabolism

  • 1500 Health Maintenance, Nutrition, and Metabolism


  • Gigliotti, Joseph C., Liberty University College of Osteopathic Medicine, Lynchburg, Virginia, United States
  • Houghton, Jeffrey F., Liberty University College of Osteopathic Medicine, Lynchburg, Virginia, United States
  • Brewer, Joseph W., Edward Via College of Osteopathic Medicine - Auburn Campus, Auburn, Alabama, United States

Previous studies have associated ERS with different forms of kidney disease, but it is unclear whether ERS influences renal physiology in normal, non-diseased states. Previous work has suggested an interaction exists between diet and ERS in other organs. Therefore, this study aimed to determine if diet alters the severity of tunicamycin (TUN)-induced ERS in male C57Bl/6 mice.


Weanling male C57Bl/6 mice were randomly assigned to receive one of three diets: chow, commercially available Western Diet (WD), or a novel Americanized diet (AD) formulated to match 50th percentile nutrient intake in humans. After 6-weeks, mice were injected with TUN (1 mg/kg, IP), or saline, to induce ERS. 24-hours later, mice were euthanized, and plasma and kidneys were collected. Plasma BUN and creatinine were quantified using commercially available assays and mRNA expression of ERS-related genes was quantified using commercially available PCR arrays. All data were analyzed using GLM procedures and significance identified with P<0.05.


Mice fed the WD had the greatest body weight and adiposity (P≤0.002). TUN alone did not influence either measure, but a significant diet*TUN interaction was observed where only mice fed WD had a 20% reduction in body weight and adiposity (P≤0.01) with TUN. TUN reduced (P<0.001) BUN (20.6±0.7 mg/dL) as compared to control mice (28.0±0.0.8), and a diet*TUN interaction was observed with mice fed AD having lower (P<0.001) BUN with TUN. Diet alone had no effect on BUN (P=0.3), but plasma creatinine was higher in mice fed AD regardless of TUN (0.65±0.04 mg/dL, P=0.005). Neither diet or TUN influenced renal inflammation by CD45+ mRNA expression. Diet alone significantly (P<0.05) influenced the expression of 30% (26 of 84) of the quantified ERS-related genes, and a significant diet*TUN interaction was observed in 14 genes. Generally, mice fed the AD had greater change in ERS-related genes with TUN.


These data highlight an interaction between diet and ERS on renal function in a non-disease setting. Our data suggest that diet, formulated to model typical American intakes, modulates the expression of ERS-related genes. Further studies are needed to validate these findings and understand their physiologic significance.