Roles of hepatic Dishevelled/Egl-10/pleckstrin domain-containing protein 5/mammalian target of rapamycin complex 1 signaling axis on the development of non-alcoholic fatty liver disease

XU Lin; XIONG Xi-Wen; LI Zun; HUANG Rong; MA Hong-Hui; MA Jie

doi:10.16098/j.issn.0529-1356.2024.03.006

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Acta Anatomica Sinica ›› 2024, Vol. 55 ›› Issue (3) : 295-301. DOI: 10.16098/j.issn.0529-1356.2024.03.006

Roles of hepatic Dishevelled/Egl-10/pleckstrin domain-containing protein 5/mammalian target of rapamycin complex 1 signaling axis on the development of non-alcoholic fatty liver disease

XU Lin^1,4* XIONG Xi-wen^2,4 LI Zun^3,4 HUANG Rong^3,4 MA Hong-hui^3,4 MA Jie^2,4

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Abstract

Objective To investigate the effect of hepatic Dishevelled/Egl-10/pleckstrin domain-containing protein 5(DEPDC5)/mammalian target of rapamycin complex 1(mTORC1) on nonalcoholic fatty liver disease by establishing a high-fat diet feeding model of Depdc5 gene hepatocyte specific knockout mice. Methods Depdc5flox/flox mice were constructed and mated with Alumin-Cre mice to obtain Depdc5flox/flox;Alb-Cre mice (LKO), Depdc5flox/flox mice were as control (Loxp). Totally 32 male mice aged 2-3 months were randomly divided into high-fat-diet LKO group, high-fat-diet Loxp control group, high-fat-diet + rapamycin LKO group, and high-fat-diet + rapamycin Loxp control group, with 8 mice in each group. Liver serum biochemistry, lipid content, protein, mRNA and pathological sections were detected; Graphpad prism 8 software was used for statistical analysis. Results High-fat-diet induced liver steatosis in Loxp mice, while LKO mice were protected from steatosis but had aggravated liver injury. Rapamycin treatment attenuated the hyperactivation of mTORC1 pathway caused by Depdc5 knockout, alleviated the liver steatosis in Loxp mice and liver injury in LKO mice. Conclusion Deletion of Depdc5 gene protects mice from high-fat-diet induced liver steatosis and rapamycin treatment might be used to improve liver injury caused by DEPDC5 loss of function.

Key words

Dishevelled/Egl-10/pleckstrin containing protein 5

/ Mammalian target of rapamycin complex 1 / High-fat-diet / Rapamycin / Nonalcoholic fatty liver / Western blotting / Mouse

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XU Lin XIONG Xi-wen LI Zun HUANG Rong MA Hong-hui MA Jie. Roles of hepatic Dishevelled/Egl-10/pleckstrin domain-containing protein 5/mammalian target of rapamycin complex 1 signaling axis on the development of non-alcoholic fatty liver disease[J]. Acta Anatomica Sinica. 2024, 55(3): 295-301 https://doi.org/10.16098/j.issn.0529-1356.2024.03.006

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