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SIRT1 mediates the role of RNA-binding protein QKI 5 in the synthesis of triglycerides in non-alcoholic fatty liver disease mice via the PPARα/FoxO1 signaling pathway

  • Authors:
    • Weiyan Zhang
    • Yue Sun
    • Wei Liu
    • Jinling Dong
    • Jinglong Chen
  • View Affiliations / Copyright

    Affiliations: Department of Infectious Disease, Huaxin Hospital, The First Hospital of Tsinghua University, Beijing 100016, P.R. China, Department of Infectious Disease, First People's Hospital Affiliated to Huzhou University Medical College, Huzhou, Zhejiang 313000, P.R. China, Department of Oncology, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1271-1280
    |
    Published online on: January 10, 2019
       https://doi.org/10.3892/ijmm.2019.4059
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Abstract

Non‑alcoholic fatty liver disease (NAFLD) is the consequence of insulin resistance, fatty acid accumulation, oxidative stress and lipotoxicity. The present study aimed to elucidate the effect of Quaking 5 (QKI 5) as mediated by Sirtuin 1 (SIRT1) on triglyceride (TG) synthesis in the liver of an NAFLD mouse model. A high‑fat diet‑induced NAFLD model was established in mice, and mouse hepatocytes were isolated to characterize the effects of QKI 5 mediated by SIRT1 on TG synthesis in the liver. Body weight and liver wet weight were recorded. In addition, serum levels of total cholesterol, TG, alanine aminotransferase and aspartate aminotransferase were assessed using an automatic biochemistry analyzer. Hematoxylin and eosin staining was performed to observe the histological morphological alterations of the liver tissues. The concentration of SIRT1 in the serum was also detected. The NAFLD activity score (NAS) was used to evaluate disease severity. The synthesis of TGs in cells or tissues was determined, and the protein levels of SIRT1, QKI 5, peroxisome proliferator‑activated receptor (PPAR)α and Forkhead box protein O1 (FoxO1) were examined. The expression levels of SIRT1 or QKI 5, and the acetylation level of QKI 5 were decreased in the mouse model of NAFLD. QKI 5 was deacetylated by SIRT1, which contributed in suppressing the progression of NAFLD in the mice, and inhibiting TG synthesis in vivo and in vitro via the PPARα/FoxO1 signaling pathway. Taken together, the results of the present study demonstrated that SIRT1 deacetylated QKI 5, an RNA‑binding protein significantly affecting the synthesis of TG in the liver of the NAFLD mouse model. Furthermore, it activated transcription factor FOXO1 through post‑transcriptional regulation of the expression of PPARα and further inhibited the synthesis of TGs, thereby restraining the progression of NAFLD.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang W, Sun Y, Liu W, Dong J and Chen J: SIRT1 mediates the role of RNA-binding protein QKI 5 in the synthesis of triglycerides in non-alcoholic fatty liver disease mice via the PPARα/FoxO1 signaling pathway. Int J Mol Med 43: 1271-1280, 2019.
APA
Zhang, W., Sun, Y., Liu, W., Dong, J., & Chen, J. (2019). SIRT1 mediates the role of RNA-binding protein QKI 5 in the synthesis of triglycerides in non-alcoholic fatty liver disease mice via the PPARα/FoxO1 signaling pathway. International Journal of Molecular Medicine, 43, 1271-1280. https://doi.org/10.3892/ijmm.2019.4059
MLA
Zhang, W., Sun, Y., Liu, W., Dong, J., Chen, J."SIRT1 mediates the role of RNA-binding protein QKI 5 in the synthesis of triglycerides in non-alcoholic fatty liver disease mice via the PPARα/FoxO1 signaling pathway". International Journal of Molecular Medicine 43.3 (2019): 1271-1280.
Chicago
Zhang, W., Sun, Y., Liu, W., Dong, J., Chen, J."SIRT1 mediates the role of RNA-binding protein QKI 5 in the synthesis of triglycerides in non-alcoholic fatty liver disease mice via the PPARα/FoxO1 signaling pathway". International Journal of Molecular Medicine 43, no. 3 (2019): 1271-1280. https://doi.org/10.3892/ijmm.2019.4059
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang W, Sun Y, Liu W, Dong J and Chen J: SIRT1 mediates the role of RNA-binding protein QKI 5 in the synthesis of triglycerides in non-alcoholic fatty liver disease mice via the PPARα/FoxO1 signaling pathway. Int J Mol Med 43: 1271-1280, 2019.
APA
Zhang, W., Sun, Y., Liu, W., Dong, J., & Chen, J. (2019). SIRT1 mediates the role of RNA-binding protein QKI 5 in the synthesis of triglycerides in non-alcoholic fatty liver disease mice via the PPARα/FoxO1 signaling pathway. International Journal of Molecular Medicine, 43, 1271-1280. https://doi.org/10.3892/ijmm.2019.4059
MLA
Zhang, W., Sun, Y., Liu, W., Dong, J., Chen, J."SIRT1 mediates the role of RNA-binding protein QKI 5 in the synthesis of triglycerides in non-alcoholic fatty liver disease mice via the PPARα/FoxO1 signaling pathway". International Journal of Molecular Medicine 43.3 (2019): 1271-1280.
Chicago
Zhang, W., Sun, Y., Liu, W., Dong, J., Chen, J."SIRT1 mediates the role of RNA-binding protein QKI 5 in the synthesis of triglycerides in non-alcoholic fatty liver disease mice via the PPARα/FoxO1 signaling pathway". International Journal of Molecular Medicine 43, no. 3 (2019): 1271-1280. https://doi.org/10.3892/ijmm.2019.4059
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