Ascorbic acid attenuates cell stress by activating the fibroblast growth factor 21/fibroblast growth factor receptor 2/adiponectin pathway in HepG2 cells

  • Authors:
    • Xinqian Gu
    • Xiao Luo
    • Yanxin Wang
    • Zhangya He
    • Xiaomin Li
    • Kunjin Wu
    • Yifan Zhang
    • Yafeng Yang
    • Jing Ji
    • Xiaoqin Luo
  • View Affiliations

  • Published online on: July 2, 2019     https://doi.org/10.3892/mmr.2019.10457
  • Pages: 2450-2458
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Abstract

Increasing prevalence of obesity‑induced non‑alcoholic fatty liver disease (NAFLD) and non‑alcoholic steatohepatitis (NASH) has been reported. Ascorbic acid (AA), also known as vitamin C, an excellent antioxidant, has been shown to exert beneficial effects on NAFLD; however, the underlying mechanisms are yet to be fully elucidated. In the present study, the role of AA on cell stress in tumor necrosis factor α (TNFα)‑treated HepG2 cells was investigated. Our findings revealed that exposure to AA effectively ameliorated TNFα‑induced cell stresses, including hypoxia, inflammation and endoplasmic reticulum (ER) stress by reducing the expression of Hif1α and its target genes (glucose transporter 1), pro‑inflammatory genes (monocyte chemoattractant 1) and ER stress‑related genes (glucose‑regulated protein, 78 kDa). AA also decreased the protein level of HIF1α. Additionally, AA significantly increased the secretion of total adiponectin and high molecular weight (HMW) adiponectin. Mechanistically, AA was determined to increase the expression of fibroblast growth factor 21 (FGF21) and its receptor, fibroblast growth factor receptor 2 (FGFR2). Knockdown of FGFR2 not only decreased the levels of total adiponectin and HMW adiponectin, but almost abolished the beneficial effects of AA in ameliorating cell stress. Collectively, the findings of our study demonstrated that AA may attenuate hepatocyte stress induced by TNFα via activation of the FGF21/FGFR2/adiponectin pathway. This could a novel mechanism of action of AA, and its potential for the treatment of NAFLD/NASH.

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September 2019
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Copy and paste a formatted citation
APA
Gu, X., Luo, X., Wang, Y., He, Z., Li, X., Wu, K. ... Luo, X. (2019). Ascorbic acid attenuates cell stress by activating the fibroblast growth factor 21/fibroblast growth factor receptor 2/adiponectin pathway in HepG2 cells. Molecular Medicine Reports, 20, 2450-2458. https://doi.org/10.3892/mmr.2019.10457
MLA
Gu, X., Luo, X., Wang, Y., He, Z., Li, X., Wu, K., Zhang, Y., Yang, Y., Ji, J., Luo, X."Ascorbic acid attenuates cell stress by activating the fibroblast growth factor 21/fibroblast growth factor receptor 2/adiponectin pathway in HepG2 cells". Molecular Medicine Reports 20.3 (2019): 2450-2458.
Chicago
Gu, X., Luo, X., Wang, Y., He, Z., Li, X., Wu, K., Zhang, Y., Yang, Y., Ji, J., Luo, X."Ascorbic acid attenuates cell stress by activating the fibroblast growth factor 21/fibroblast growth factor receptor 2/adiponectin pathway in HepG2 cells". Molecular Medicine Reports 20, no. 3 (2019): 2450-2458. https://doi.org/10.3892/mmr.2019.10457