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Sulforaphane modulates CX3CL1/CX3CR1 axis and inflammation in palmitic acid-induced cell injury in C2C12 skeletal muscle cells

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Abstract

Studies have shown that sulforaphane (SFN) has potent anti-inflammatory and free radical scavenging effects on obesity and associated disorder such as diabetes, polycystic ovary syndrome, and metabolic syndrome. fractalkine (CX3CL1) and its receptor, CX3CR1, play an important role in muscle metabolism by improving insulin-sensitizing effects. Here, in this study we examined the SFN effect on CX3CL1 and its receptor, CX3CR1, in C2C12 myotubes in palmitic acid (PA)-induced oxidative stress and inflammation. The results showed that PA (750 μM) evoked lipotoxicity as a reduction in cell viability, increased IL-6 and TNF-α expression, and enhanced reactive oxygen species (ROS). However, SFN pretreatment attenuated the levels of, IL-6 and TNF-α in C2C12 myotubes exposure to PA. Moreover, SFN pretreatment up-regulated nuclear factor erythroid related factor 2 (Nrf2) /heme oxygenase-1(HO-1) pathway protein in C2C12 cells as indicated by a decrease in ROS levels. Interestingly, PA also caused an increase in CX3CL1 and CX3CR1 expression that SFN abrogated it. We also found the protective effect of SFN agonist PA-induced lipotoxicity with promotes in UCP3 gene expression in C2C12 cells. Collectively, these findings suggest that SFN hampers the PA-induced inflammation in C2C12 cells by modulation of the Nrf2/HO-1 pathway and CX3CL1/CX3CR1 axis and may propose a new therapeutic approach to protect against obesity-associated disorders in skeletal muscle cells.

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Acknowledgements

The authors thank the Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran, for all support provided.

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Authors and Affiliations

  1. Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Yousef Faridvand, Samad Ghaffari, Mohammad Nouri & Ahmadreza Jodati

  2. Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Yousef Faridvand & Hamid Reza Nejabati

  3. Department of Biochemistry, Faculty of Sciences, Tabriz University, Tabriz, Iran

    Parinaz Haddadi & Elham Zamani-Gharehchamani

  4. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran

    Samira Nozari

  5. Stem Cells Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Samira Nozari & Mohammad Nouri

  6. Stem Cell and Regenerative Medicine (SCARM) Institute, Tabriz University of Medical Sciences, Tabriz, Iran

    Mohammad Nouri

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  1. Yousef Faridvand
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All authors, YF, PH, HRN, SG, EZ, SN, MN, and AJ have participated in conception and design, analysis, interpretation of the data, drafting the article, revising article critically for important intellectual content and approval for the final version and submission.

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Correspondence to Mohammad Nouri or Ahmadreza Jodati.

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Faridvand, Y., Haddadi, P., Nejabati, H.R. et al. Sulforaphane modulates CX3CL1/CX3CR1 axis and inflammation in palmitic acid-induced cell injury in C2C12 skeletal muscle cells. Mol Biol Rep 47, 7971–7977 (2020). https://doi.org/10.1007/s11033-020-05875-9

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  • DOI: https://doi.org/10.1007/s11033-020-05875-9

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