当前位置： SCI文献检索 > INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE期刊下所有文献 > 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.

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.

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.

journal_name

Int J Mol Med

journal_title

International journal of molecular medicine

authors

Zhang W,Sun Y,Liu W,Dong J,Chen J

doi

10.3892/ijmm.2019.4059

subject

Has Abstract

pub_date

2019-03-01 00:00:00

pages

1271-1280

issue

eissn

1107-3756

issn

1791-244X

journal_volume

pub_type

杂志文章

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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.