Cdh1 plays a protective role in nonalcoholic fatty liver disease by regulating PPAR/PGC-1α signaling pathway

Background: Nonalcoholic fatty liver disease (NAFLD) is a significant etiological factor in liver-related diseases, which can lead to severe consequences such as steatohepatitis, cirrhosis and death. Cdh1 is considered as a crucial protein involved in cell cycle regulation. The purpose of this study is to explore the biological role of Cdh1 in NAFLD.Materials and methods: NAFLD cell model was established, and L02 cells and AML12 cells were infected by shRNA lentivirus with Cdh1 knockdown in vitro, and the effect of Cdh1 deletion on cell lipid deposition was evaluated. The effects of Cdh1 deletion on Akt phosphorylation and PPAR/PGC-1 alpha signaling pathway in L02 cells were examined. In addition, the NAFLD mouse model was constructed, and the conditional knockout mice of Cdh1 were selected to verify the results.Results: In vitro experiments showed that the Cdh1 deletion enhanced cell lipid deposition. In vivo experiments showed that conditional knockdown of Cdh1 aggravated fatty degeneration and damage of liver in mice. Cdh1 deletion promotes Akt phosphorylation and inhibits PPAR/PGC-1 alpha signaling pathway in L02 cells. Conditional knockout of Cdh1 down-regulates PPAR/PGC-1 alpha signaling pathway in NAFLD mouse model.Conclusion: The deletion of Cdh1 may promote Akt phosphorylation by up-regulating Skp2 and inhibit the PPAR/ PGC-1 alpha signaling pathway. Cdh1 serves a protective function in the occurrence and progression of NAFLD.

Automated summary

This study found that the deletion of the Cdh1 gene may contribute to the occurrence and progression of NAFLD by promoting Akt phosphorylation and inhibiting the PPAR/PGC-1 alpha signaling pathway. The results of this study are of great significance for a better understanding of the pathogenesis of NAFLD and the development of related therapeutic strategies.