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Trimethylamine-N-oxide, a New Risk Factor for Non-alcoholic Fatty Liver Disease Changes the Expression of miRNA-34a, and miRNA-122 in the Fatty Liver Cell Model

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Abstract

Non-alcoholic fatty liver disease is a multifactorial disorder with complicated pathophysiology ranging from simple steatosis to steatohepatitis and liver fibrosis. Trimethylamine-N-oxide (TMAO) production is believed to be correlated with choline deficiency. This study investigated the expression of miRNA-34a, miRNA-122, and miRNA-192 in the fatty liver cell model treated with different concentrations of TMAO. A fatty liver cell model was developed by exposing HepG2 cells to a mixture of palmitate and oleate in a ratio of 1:2 at a final concentration of 1200 μM for 24 h. The confirmed fatty liver cells were treated with 37.5, 75, 150, and 300 μM of TMAO for 24 h. RT-qPCR was used to quantify the expression of microRNAs in a cellular model. The cellular expression of all microRNAs was significantly higher in treated fatty liver cells compared to normal HepG2 cells (P < 0.05). Only 75 and 150 µM of TMAO significantly increased the expression of miRNA-34a and miRNA-122 compared to both fatty and normal control cells (P < 0.05). Our results provided an experimental documentation for the potential effect of TMAO to change the expression of miR-34a and miR-22 as a mechanism for contributing to the pathogenesis of non-alcoholic fatty liver disease.

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Data Availability

All data generated or analyzed in this study are available upon reasonable request.

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Funding

This study was conducted as a dissertation of a master's student in clinical biochemistry. The study was supported financially by vice chancellor in research of Kurdistan University of Medical Sciences [grant numbers IR.MUK.REC.1398.315].

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Authors and Affiliations

  1. Student Research Committee, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Zhila Bahramirad

  2. Department of Clinical Biochemistry, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Mohammad Moradzad & Zakaria Vahabzadeh

  3. Liver and Digestive Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Mohammad Raman Moloudi

  4. Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Alina Abdollahi & Zakaria Vahabzadeh

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  1. Zhila Bahramirad
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  2. Mohammad Raman Moloudi
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  4. Alina Abdollahi
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  5. Zakaria Vahabzadeh
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Contributions

ZB carried out the sample collection, all laboratory works, and final report preparation. MRM has given advice on the project and assisted with manuscript preparation. MM contributes to statistical analysis and writing manuscript. AA helped with sample collection. ZV carried out the design, supervised the study, and prepared the manuscript. The manuscript’s contents have been read and approved by all authors. The authors declare that they have no conflict of interest.

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Correspondence to Zakaria Vahabzadeh.

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Bahramirad, Z., Moloudi, M.R., Moradzad, M. et al. Trimethylamine-N-oxide, a New Risk Factor for Non-alcoholic Fatty Liver Disease Changes the Expression of miRNA-34a, and miRNA-122 in the Fatty Liver Cell Model. Biochem Genet (2024). https://doi.org/10.1007/s10528-024-10754-0

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