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Abstract: PO1395

Calorie Restriction Ameliorates Obesity-Related Glomerulopathy in Adult Zebrafish

Session Information

Category: Glomerular Diseases

  • 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix

Authors

  • Zeitler, Evan, UNC Kidney Center, Chapel Hill, North Carolina, United States
  • Jennette, J. Charles, UNC Kidney Center, Chapel Hill, North Carolina, United States
  • Flythe, Jennifer E., UNC Kidney Center, Chapel Hill, North Carolina, United States
  • Falk, Ronald J., UNC Kidney Center, Chapel Hill, North Carolina, United States
  • Poulton, John S., UNC Kidney Center, Chapel Hill, North Carolina, United States
Background

Obesity is a risk factor for chronic kidney disease. The mechanisms by which obesity results in kidney disease are understudied. Zebrafish are an attractive model animal for studying obesity due to their conserved biology and amenability to genetic screening. The effects of obesity on kidney function in zebrafish have not been reported.

Methods

Zebrafish were fed high-calorie and high-fat diets for 8 weeks. Kidneys were evaluated by light and electron microscopy, and the glomerular filtration barrier was assessed by fluorescent dextran permeability. We also tested the ability of calorie restriction to reverse obesity-related defects.

Results

Fish fed a high calorie diet developed glomerulomegaly, foot process effacement, GBM thickening, tubular enlargement (Figure 1) and ectopic lipid deposition after 8 weeks. High calorie feeding resulted in filtration barrier dysfunction. The observed effects resolved after 4 weeks of calorie restriction (Figure 2).

Conclusion

Our study reveals that obese zebrafish recapitulate key aspects of human pathology, and these defects can be reversed with calorie restriction. These findings establish zebrafish as a potential model for the study of obesity-related kidney disease.

ND - normal diet, HF - high fat diet, HC - high calorie diet, HCHF - high calorie+high fat diet.

ND - normal diet, HC - high calorie diet, MTN - maintenance calories, CR - calorie restriction

Funding

  • NIDDK Support