Characterizing the metabolic response of the zebrafish kidney to overfeeding.

IF 3.7 2区 医学 Q1 PHYSIOLOGY American Journal of Physiology-renal Physiology Pub Date : 2023-10-01 Epub Date: 2023-08-17 DOI:10.1152/ajprenal.00113.2023
Evan M Zeitler, Yuanyuan Li, Madison Schroder, Ronald J Falk, Susan Sumner
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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.

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描述斑马鱼肾脏对过量喂养的代谢反应。
肥胖是一种全球性流行病,也是慢性肾脏疾病发展的危险因素。肥胖会引起新陈代谢的系统性变化,但它如何具体影响肾脏代谢尚不清楚。此前,斑马鱼在喂食高热量饮食时会出现与肥胖相关的肾脏病理和功能障碍。为了了解肥胖对肾脏代谢功能的直接影响,我们对斑马鱼进行了为期8周的对照和过量喂养饮食治疗。在治疗结束时,我们评估了肾脏和鱼类重量的变化,并使用电子显微镜评估了细胞的超微结构。然后,我们使用超高效液相色谱法和高分辨率质谱法对鱼类的肾组织进行了非靶向代谢组学分析,并使用木乃伊和基因集富集分析来揭示不同影响的代谢途径。肾脏代谢组在对照饮食和过量饮食之间存在显著且一致的差异。在9593个特征中,我们发现235个特征在各组之间存在显著差异(P<0.05)(125个在过量饮食中上调,110个下调)。途径分析表明糖酵解和脂肪酸合成途径存在扰动,对特定代谢物的分析表明色氨酸代谢存在扰动。我们的关键发现表明,饮食诱导的肥胖会导致肾组织本身的代谢变化,并在肥胖相关肾病的发病机制中涉及特定的代谢途径,包括糖酵解和色氨酸代谢,这证明了非靶向代谢组学通过直接询问肾组织来识别感兴趣的途径的能力。新的和值得注意的肥胖会导致全身代谢功能障碍,但这如何影响肾脏代谢尚不清楚。本研究采用超高效液相色谱-高分辨率质谱联用技术对过量喂养的斑马鱼肾脏进行了分析。肥胖斑马鱼肾脏中的代谢产物揭示了代谢途径的紊乱,包括糖酵解和色氨酸代谢。这些数据表明,肥胖会改变肾脏内的代谢,这可能在肥胖相关的肾功能障碍中发挥重要作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
8.40
自引率
7.10%
发文量
154
审稿时长
2-4 weeks
期刊介绍: The American Journal of Physiology - Renal Physiology publishes original manuscripts on timely topics in both basic science and clinical research. Published articles address a broad range of subjects relating to the kidney and urinary tract, and may involve human or animal models, individual cell types, and isolated membrane systems. Also covered are the pathophysiological basis of renal disease processes, regulation of body fluids, and clinical research that provides mechanistic insights. Studies of renal function may be conducted using a wide range of approaches, such as biochemistry, immunology, genetics, mathematical modeling, molecular biology, as well as physiological and clinical methodologies.
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