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Updated: Jun 24, 2026
Evaluation of Zebrafish Kidney Function Using a Fluorescent Clearance Assay
Published on: February 20, 2015
Characterizing the metabolic response of the zebrafish kidney to overfeeding
Evan M Zeitler1, Yuanyuan Li2, Madison Schroder2
1Division of Nephrology and Hypertension, Department of Medicine, UNC Kidney Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States.
Abstract:
Obesity is a global epidemic and risk factor for the development of chronic kidney disease. Obesity induces systemic changes in metabolism, but how it affects kidney metabolism specifically is not known. Zebrafish have previously been shown to develop obesity-related kidney pathology and dysfunction when fed hypercaloric diets. To understand the direct effects of obesity on kidney metabolic function, we treated zebrafish for 8 wk with a control and an overfeeding diet. At the end of treatment, we assessed changes in kidney and fish weights and used electron microscopy to evaluate cell ultrastructure. We then performed an untargeted metabolomic analysis on the kidney tissue of fish using ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry and used mummichog and gene set enrichment analysis to uncover differentially affected metabolic pathways. Kidney metabolomes differed significantly and consistently between the control and overfed diets. Among 9,593 features, we identified 235 that were significantly different (P < 0.05) between groups (125 upregulated in overfed diet, 110 downregulated). Pathway analysis demonstrated perturbations in glycolysis and fatty acid synthesis pathways, and analysis of specific metabolites points to perturbations in tryptophan metabolism. Our key findings show that diet-induced obesity leads to metabolic changes in the kidney tissue itself and implicates specific metabolic pathways, including glycolysis and tryptophan metabolism in the pathogenesis of obesity-related kidney disease, demonstrating the power of untargeted metabolomics to identify pathways of interest by directly interrogating kidney tissue.NEW & NOTEWORTHY Obesity causes systemic metabolic dysfunction, but how this affects kidney metabolism is less understood. This study used ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry to analyze the kidneys of overfed zebrafish. Metabolites in the kidneys of obese zebrafish revealed perturbations in metabolic pathways including glycolysis and tryptophan metabolism. These data suggest obesity alters metabolism within the kidney, which may play an important role in obesity-related kidney dysfunction.
Insights
Diet-induced obesity alters kidney metabolism, impacting pathways like glycolysis and tryptophan metabolism. This research reveals direct metabolic changes within kidney tissue, crucial for understanding obesity-related kidney disease.
Area of Science:
- Nephrology
- Metabolomics
- Zebrafish models
Background:
- Obesity is a global epidemic and a significant risk factor for chronic kidney disease.
- Systemic metabolic changes occur in obesity, but their specific impact on kidney metabolism remains unclear.
- Zebrafish models exhibit obesity-related kidney pathology and dysfunction when fed hypercaloric diets.
Purpose of the Study:
- To investigate the direct effects of diet-induced obesity on kidney metabolic function.
- To identify specific metabolic pathways perturbed in the kidneys of obese zebrafish.
- To leverage untargeted metabolomics for understanding obesity-related kidney disease pathogenesis.
Main Methods:
- Zebrafish were fed control and overfeeding diets for 8 weeks.
- Kidney and fish weights were assessed, and kidney ultrastructure was evaluated using electron microscopy.
- Untargeted metabolomic analysis of kidney tissue was performed using ultra-high performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS).
- Metabolic pathways were analyzed using mummichog and gene set enrichment analysis.
Main Results:
- Significant differences in kidney metabolomes were observed between control and overfed groups.
- Out of 9,593 detected features, 235 were significantly different (P < 0.05), with 125 upregulated and 110 downregulated in the overfed group.
- Pathway analysis revealed significant perturbations in glycolysis and fatty acid synthesis.
- Specific metabolites indicated alterations in tryptophan metabolism.
Conclusions:
- Diet-induced obesity directly causes metabolic alterations within kidney tissue.
- Perturbations in glycolysis and tryptophan metabolism are implicated in the pathogenesis of obesity-related kidney disease.
- Untargeted metabolomics is a powerful tool for identifying key metabolic pathways in kidney tissue affected by obesity.
