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Elucidating ascorbate and aldarate metabolism pathway characteristics via integration of untargeted metabolomics and transcriptomics of the kidney of high-fat diet-fed obese mice

  • 0Department of Basic Medical Sciences, Medical College, Qinghai University, Xining, Qinghai, China.
Plos One +

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April 11, 2024

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April 11, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

High-fat diets cause obesity and kidney damage by increasing oxidative stress. This study found that obesity alters ascorbate and aldarate metabolism in mouse kidneys, with reduced ascorbate levels indicating potential kidney damage.

Area Of Science

  • Metabolomics and transcriptomics
  • Renal physiology
  • Nutritional science

Background

  • Obesity is a significant risk factor for chronic kidney disease (CKD).
  • High-fat diets induce obesity and renal oxidative stress.
  • The impact of oxidative stress on ascorbate and aldarate metabolism in the kidney is not well understood.

Purpose Of The Study

  • To investigate alterations in the ascorbate and aldarate metabolic pathway in the kidneys of obese mice.
  • To determine the effects of high-fat diet-induced obesity and oxidative stress on this pathway.
  • To identify potential biomarkers for obesity-related kidney damage.

Main Methods

  • Induction of obesity in male C57BL/6J mice using a 12-week high-fat diet.
  • Non-targeted metabolomics profiling of kidney tissues.
  • RNA sequencing for transcriptomic analysis.
  • Integrated analysis of metabolomics and transcriptomics data.

Main Results

  • High-fat diet-induced obesity led to glomerular basement membrane thinning, podocyte alterations, and increased renal oxidative stress.
  • Integrated analysis identified 2 differentially expressed genes and 13 differential metabolites in the ascorbate and aldarate pathway.
  • Downregulation of ugt1a9 and ugt2b1 gene expression and reduced kidney ascorbate levels were observed in obese mice.

Conclusions

  • Renal oxidative stress from high-fat diet-induced obesity disrupts ascorbate and aldarate metabolic regulation.
  • Reduced ascorbate levels in kidney tissue may serve as a predictive marker for kidney damage in obesity.
  • Understanding these metabolic changes is crucial for developing strategies to prevent or treat obesity-related CKD.