Transcriptome Analysis of the Effect of Nickel on Lipid Metabolism in Mouse Kidney

TL;DR

Nickel exposure harms mouse kidneys by disrupting lipid metabolism and increasing oxidative stress and inflammation.

Contribution

This study reveals how nickel suppresses lipid metabolism genes and AMPK/PPAR pathways in the kidney.

Findings

Nickel stress increased blood glucose and lipid indicators by 50-200% in ICR mice.

Nickel elevated oxidative stress and inflammation markers in the kidney by about 30%.

Nickel inhibited genes related to lipid metabolism and the AMPK and PPAR signaling pathways.

Abstract

Lipid and glucose metabolism are intimately linked to many disorders, however, further research is needed to understand how they contribute to damage caused by nickel. According to our research, nickel stress increased the levels of blood glucose and lipid indicators. In addition, oxidative stress and inflammation in the kidney were elevated by nickel stress. We identified and examined the differently expressed genes in the kidney caused by nickel stress using RNA sequencing. Nickel suppressed the expression of genes linked to lipid metabolism as well as the AMPK and PPAR signaling pathways in the kidney, according to bioinformatics analysis and experimental verification.

Although the human body needs nickel as a trace element, too much nickel exposure can be hazardous. The effects of nickel on cells include inducing oxidative stress, interfering with DNA damage repair, and altering epigenetic modifications. Glucose metabolism and lipid metabolism are closely related to oxidative stress; however, their role in nickel-induced damage needs further study. In Institute of Cancer Research (ICR) mice, our findings indicated that nickel stress increased the levels of blood lipid indicators (triglycerides, high-density lipoprotein, and cholesterol) by about 50%, blood glucose by more than two-fold, and glycated serum protein by nearly 20%. At the same time, nickel stress increased oxidative stress (malondialdehyde) and inflammation (Interleukin 6) by about 30% in the kidney. Based on next-generation sequencing technology, we detected and analyzed differentially expressed genes in the kidney caused by nickel stress. Bioinformatics analysis and experimental verification showed that nickel inhibited the expression of genes related to lipid metabolism and the AMPK and PPAR signaling pathways. The finding that nickel induces kidney injury and inhibits key genes involved in lipid metabolism and the AMPK and PPAR signaling pathways provides a theoretical basis for a deeper understanding of the mechanism of nickel-induced kidney injury.

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