Abstract: TH-PO938
Characterizing the Metabolic Response of the Zebrafish Kidney to a High-Calorie Diet
Session Information
- Health Maintenance, Nutrition, Metabolism - I
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Health Maintenance, Nutrition, and Metabolism
- 1500 Health Maintenance, Nutrition, and Metabolism
Authors
- Zeitler, Evan, The University of North Carolina at Chapel Hill Kidney Center, Chapel Hill, North Carolina, United States
- Falk, Ronald, The University of North Carolina at Chapel Hill Kidney Center, Chapel Hill, North Carolina, United States
- Sumner, Susan Jenkins, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
Group or Team Name
- UNC Kidney Center.
Background
Obesity is an epidemic risk factor for the development of chronic kidney disease. Obesity induces systemic changes in metabolism; its effect on kidney metabolism specifically is not known.
Methods
We treated zebrafish for 8 weeks with a control (ND) and a high calorie (HC) diet and performed an untargeted metabolomic analysis on the kidney tissue of fish using ultra-high performance liquid chromatography coupled mass spectrometry. We used mummichog and gene set enrichment analysis to uncover differentially affected metabolic pathways.
Results
Overfed zebrafish were heavier and had larger kidneys. Kidney metabolomes differed significantly (Figure 1A), and 235 metabolites were significantly different between groups (125 upregulated in high calorie diet, 110 downregulated) (Figure 1B). Analysis of specific metabolites suggested alterations in tryptophan metabolism, purinergic signaling and fatty acid oxidation (Figure 1C-E). Pathway analysis demonstrated alterations in metabolic pathways including glycolysis and fatty acid synthesis (Figure 2A-B).
Conclusion
Our findings show that diet induced obesity leads to metabolic changes in the kidney tissue and implicate 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.