Effect of hyodeoxycholic acid on the activity of steatosis hepatocytes and its mechanism

Yuanyuan WANG; Yan ZOU; Zhaoxia LIU; Xuefeng YANG

doi:10.12449/JCH240212

Volume 40 Issue 2

Feb. 2024

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Article Navigation > Journal of Clinical Hepatology > 2024 > 40(2): 292-297

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Effect of hyodeoxycholic acid on the activity of steatosis hepatocytes and its mechanism

DOI: 10.12449/JCH240212

Yuanyuan WANG^{1a, 2},
Yan ZOU^1b,
Zhaoxia LIU^{1a, 2},
Xuefeng YANG^{1a, 2
,
,
,}

1a.
Department of Gastroenterology，Nanhua Hospital Affiliated to University of South China，Hengyang，Hunan 421002，China
1b.
Department of Hand and Foot Surgery，Nanhua Hospital Affiliated to University of South China，Hengyang，Hunan 421002，China
2.
Hunan Provincial Clinical Research Center for Metabolic Associated Fatty Liver Disease，Hengyang，Hunan 421002，China

Research funding:

General Project of Hunan Provincial Education Department (20C1586);

Hunan Provincial Science and Technology Innovation Program Project (2020SK51910);

Hunan Provincial Science and Technology Innovation Program Project (2021SK51902)

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Corresponding author: YANG Xuefeng， yxf009988@sina.com （ORCID： 0000-0002-3470-0350）
Received Date: 2023-05-08
Accepted Date: 2023-06-09
Published Date: 2024-02-19

Abstract

Abstract

Objective To investigate the role and mechanism of hyodeoxycholic acid （HDCA） in the progression of metabolic associated fatty liver disease （MAFLD）， and to provide a new theoretical basis for further clarifying the pathogenesis of MAFLD. Methods L02 hepatocytes were used as experimental cells， and palmitic acid was used to induce steatosis in L02 cells. The farnesoid X receptor （FXR） siRNA interference chain technique was used to construct a hepatocyte cell line with low FXR expression. CCK8 assay was used to observe the effect of HDCA on L02 steatosis hepatocytes at different concentrations （0， 100， 200， 300， and 400 μmol/L） and time points （12， 24， 36， and 48 hours）. The method of qRT-PCR was used to measure the mRNA expression levels of FXR， proliferating cell nuclear antigen （PCNA）， Cyclin D1， phosphatidylinositol 3-kinase （PI3K）， and protein kinase-B （AKT）， and Western blot was used to measure the protein expression levels of FXR， Cyclin D1， PCNA， PI3K， phosphorylated PI3K （p-PI3K）， AKT， and phosphorylated （p-AKT）. A one-way analysis of variance was used for comparison of normally distributed continuous data with homogeneity of variance between multiple groups， and the Tukey HSD test was used for further comparison between two groups； the Welch analysis of variance was used for comparison of normally distributed continuous data with heterogeneity of variance between multiple groups， and the Games-Howell test was used for further comparison between two groups. The independent-samples t test was used for comparison between two groups. Results CCK8 assay showed a significant reduction in the viability of L02 cells and steatosis hepatocytes treated by 300 μmol/L HDCA （P<0.05）， and qRT-PCR showed a significant increase in the mRNA expression level of FXR and significant reductions in the mRNA expression levels of PCNA， Cyclin D1， PI3K， and AKT （all P<0.05）. Western blot showed a significant increase in the protein expression level of FRX （P<0.05）， and after interference of FXR expression in L02 cells， there were significant increases in the protein expression levels of PCNA， PI3K， p-PI3K， AKT， and p-AKT （all P<0.05）. Conclusion HDCA inhibits the PI3K/AKT signaling pathway by upregulating FXR expression， thereby inducing a reduction in the viability of steatosis hepatocytes.
- Metabolism-Associated Fatty Liver Disease,
- Hyodeoxycholic Acid,
- Farnesoid X Receptor

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References(30)

References

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Effect of hyodeoxycholic acid on the activity of steatosis hepatocytes and its mechanism

DOI: 10.12449/JCH240212

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Effect of hyodeoxycholic acid on the activity of steatosis hepatocytes and its mechanism

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