PUBLICATION
High calorie diet results in reversible obesity-related glomerulopathy in adult zebrafish regardless of dietary fat
- Authors
- Zeitler, E.M., Jennette, J.C., Flythe, J.E., Falk, R.J., Poulton, J.S.
- ID
- ZDB-PUB-220302-14
- Date
- 2022
- Source
- American journal of physiology. Renal physiology 322(5): F527-F539 (Journal)
- Registered Authors
- Keywords
- animal model, diet, obesity, obesity-related glomerulopathy, zebrafish
- MeSH Terms
-
- Animals
- Diet
- Dietary Fats
- Glomerular Basement Membrane/pathology
- Kidney Diseases*/etiology
- Kidney Diseases*/pathology
- Obesity/complications
- Obesity/pathology
- Zebrafish*
- PubMed
- 35224994 Full text @ Am. J. Physiol. Renal Physiol.
Citation
Zeitler, E.M., Jennette, J.C., Flythe, J.E., Falk, R.J., Poulton, J.S. (2022) High calorie diet results in reversible obesity-related glomerulopathy in adult zebrafish regardless of dietary fat. American journal of physiology. Renal physiology. 322(5):F527-F539.
Abstract
Obesity is a risk factor for the development of kidney disease. The role of diet in this association remains undetermined, in part due to practical limitations in studying nutrition in humans. In particular, the relative importance of calorie excess versus dietary macronutrient content is poorly understood. For example, it is unknown if calorie restriction modulates obesity-related kidney pathology. To study the effects of diet-induced obesity in a novel animal model, we treated zebrafish for 8 weeks with diets varied in both calorie and fat content. Kidneys were evaluated by light and electron microscopy. We evaluated glomerular filtration barrier function using a dextran permeability assay. We assessed the effect of diet on podocyte sensitivity to injury using an inducible podocyte injury model. We then tested the effect of calorie restriction on the defects caused by diet-induced obesity. Fish fed a high calorie diet developed glomerulomegaly (mean=1211 µm2 versus 1010 µm2 in controls, p=0.007), lower podocyte density, foot process effacement, GBM thickening, tubular enlargement (mean=1038 µm2 versus 717 µm2 in controls, p<0.0001), and ectopic lipid deposition. Glomerular filtration barrier dysfunction and increased susceptibility to podocyte injury were observed with high calorie feeding regardless of dietary fat content. These pathologic changes resolved with 4 weeks of calorie restriction. Our findings suggest that calorie excess rather than dietary fat drives obesity-related kidney dysfunction and that inadequate podocyte proliferation in response to glomerular enlargement may cause podocyte dysfunction. We demonstrate the value of zebrafish as a novel model for studying diet in obesity-related kidney disease.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping