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. 2021 Jun;476(6):2527-2538.
doi: 10.1007/s11010-020-03990-6. Epub 2021 Feb 26.

Endoplasmic reticulum stress and autophagy are involved in adipocyte-induced fibrosis in hepatic stellate cells

Yingjuan Liu  1   2 , Xiaolin Wu  1 , Yue Wang  1 , Yunliang Guo  3   4
Affiliations

Endoplasmic reticulum stress and autophagy are involved in adipocyte-induced fibrosis in hepatic stellate cells

Yingjuan Liu et al. Mol Cell Biochem. 2021 Jun.

Abstract

Liver fibrosis, with the characterization of progressive accumulation of extracellular matrix (ECM), is the common pathologic feature in the process of chronic liver disease. Hepatic stellate cells (HSCs) which are activated and differentiate into proliferative and contractile myofibroblasts are recognized as the main drivers of fibrosis. Obesity-related adipocytokine dysregulation is known to accelerate liver fibrosis progression, but the direct fibrogenic effect of mature adipocytes on HSCs has been rarely reported. Therefore, the purpose of this study was to explore the fibrogenic effect of adipocyte 3T3-L1 cells on hepatic stellate LX-2 cells. The results showed that incubating LX-2 cells with the supernatant of 3T3-L1 adipocytes triggered the expression of ECM related proteins, such as α-smooth muscle actin (α-SMA), type I collagen (CO-I), and activated TGF β/Smad2/3 signaling pathway in LX-2 cells. In addition, 3T3-L1 cells inhibited insulin sensitivity, activated endoplasmic reticulum stress and autophagy to promote the development of fibrosis. These results supported the notion that mature adipocytes can directly activate hepatic stellate cells, and the establishment of an in vitro model of adipocytes on HSCs provides an insight into screening of drugs for liver diseases, such as nonalcoholic fatty liver disease.

Keywords: 3T3-L1 cells; Autophagy; Endoplasmic reticulum stress; Fibrosis; LX-2 cells.

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References

    1. Sato T, Vargas D, Miyazaki K, Uchida K, Ariyani W, Miyazaki M, Okada J, Lizcano F, Koibuchi N, Shimokawa N (2020) EID1 suppresses lipid accumulation by inhibiting the expression of GPDH in 3T3-L1 preadipocytes. J Cell Physiol. https://doi.org/10.1002/jcp.29567 - DOI - PubMed
    1. Azzu V, Vacca M, Virtue S, Allison M, Vidal-Puig A (2020) Adipose tissue-liver cross talk in the control of whole-body metabolism: implications in non-alcoholic fatty liver disease. Gastroenterology. https://doi.org/10.1053/j.gastro.2019.12.054 - DOI - PubMed
    1. Bluher M (2020) Metabolically healthy obesity. Endocr Rev. https://doi.org/10.1210/endrev/bnaa004 - DOI - PubMed - PMC
    1. Cordeiro A, Costa R, Andrade N, Silva C, Canabrava N, Pena MJ, Rodrigues I, Andrade S, Ramalho A (2020) Does adipose tissue inflammation drive the development of non-alcoholic fatty liver disease in obesity? Clin Res Hepatol Gastroenterol. https://doi.org/10.1016/j.clinre.2019.10.001 - DOI - PubMed
    1. Rom O, Xu G, Guo Y, Zhu Y, Wang H, Zhang J, Fan Y, Liang W, Lu H, Liu Y, Aviram M, Liu Z, Kim S, Liu W, Wang X, Chen YE, Villacorta L (2019) Nitro-fatty acids protect against steatosis and fibrosis during development of nonalcoholic fatty liver disease in mice. EBioMedicine 41(2019):62–72. https://doi.org/10.1016/j.ebiom.2019.02.019 - DOI - PubMed - PMC

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