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Updated: Mar 3, 2026
Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Integrated transcriptome-metabolome analysis reveals attenuated combined toxicity: antagonistic interactions of three
Miao Zhang1, Chenxu Wang1, Lin Zhu1
1Institute of Food and Nutraceutical Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, China.
Abstract:
To investigate the toxicological effects after individual or combined sub-chronical exposure to oxidized triacylglycerols, aldehydes, and 3-MCPDE formed during thermal processing of high-fat foods, this study implemented transcriptome-metabolome analysis of renal tissues in Kunming mice, supplemented with urine metabolomics study. Transcriptomic analysis highlighted perturbations in the PI3K-Akt signaling pathway, while metabolomic and integrated analyses both identified disruptions in glycerophospholipid metabolism. Urine metabolomic results further corroborated renal dysfunction, with altered tryptophan and purine metabolism. Results revealed that the exposure of three toxicants induced multi-organ metabolic network encompassing the kidney, liver, and even nervous system. Toxic effects were less pronounced when the three toxicants were exposed in combination while compared to their individual effects, suggesting the necessity for further investigation in the potential antagonistic mechanisms. Results provide critical insights into the co-exposure toxicity and interaction mechanisms of thermally induced toxicants in high-fat foods, offering toxicological foundations for establishing safety regulations.
Insights
This study investigated toxic effects from high-fat food compounds. Combined exposure to oxidized triacylglycerols, aldehydes, and 3-MCPDE showed less harm than individual exposure, indicating potential antagonistic effects.
Area of Science:
- Toxicology
- Food Chemistry
- Metabolomics
Background:
- Thermal processing of high-fat foods generates toxicants like oxidized triacylglycerols, aldehydes, and 3-monochloropropane-1,2-diol esters (3-MCPDE).
- Sub-chronic exposure to these compounds can pose health risks, necessitating toxicological investigation.
Purpose of the Study:
- To investigate the toxicological effects of individual and combined exposure to oxidized triacylglycerols, aldehydes, and 3-MCPDE.
- To elucidate the metabolic and transcriptomic alterations in renal tissues and urine.
Main Methods:
- Transcriptome-metabolome analysis of renal tissues in Kunming mice.
- Supplementation with urine metabolomics study.
- Investigated individual and combined exposure scenarios.
Main Results:
- Transcriptomic analysis revealed perturbations in the PI3K-Akt signaling pathway.
- Metabolomic and integrated analyses identified disruptions in glycerophospholipid metabolism.
- Urine metabolomics indicated renal dysfunction, with altered tryptophan and purine metabolism.
Conclusions:
- Exposure to these toxicants induces a multi-organ metabolic network disruption affecting the kidney, liver, and nervous system.
- Combined exposure exhibited less pronounced toxic effects compared to individual exposure, suggesting antagonistic mechanisms.
- Provides insights into co-exposure toxicity and interaction mechanisms of thermally induced toxicants, informing safety regulations.
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