Y-box binding protein 1 regulates liver lipid metabolism by regulating the Wnt/β-catenin signaling pathway

Abstract

Background: We mainly investigated how y-box binding protein 1 (YB-1) regulates liver lipid metabolism through the Wnt/β-catenin signaling pathway using multiple models.Methods: The LO2 cells were treated with palmitic acid (PA) to create an NAFLD model in vitro.Immunohistochemistry and Western blotting assays were used to detect the expression of YB-1, β-Catenin, SREBP-1c, LXRa, FXR1 and PPARα protein, and RNAs of them was detected by qRT-PCR. Oil Red O assay was applied to observe lipid droplets in LO2 cells and liver tissues. H&E staining was performed to observe the degree of liver inflammation. Proteomics in LO2 cells were conducted by Tandem mass tag proteomics assay. Co-immunoprecipitation and Western blotting assays were used to verify YB-1 complexed pGSK3β.ELISA and Western blotting assays were used to detect the concentrations of TNFα and IL-6 in supernates of LO2 cells and liver tissues, respectively.Results: We found that YB-1 and β-catenin were highly expressed in the LO2 cell NAFLD model, and that the expression of TNFα and IL-6 also increased. Lipid synthases (SREBP-1c and LXRa) expression were decreased, while β-oxidation-related factors (FXR1 and PPARα) expression were increased. The expression of SREBP-1c and LXRa were increased while FXR1 and PPARα were decreased, though such responses were rescued through inhibiting β-catenin expression. Finally, tandem mass tag proteomics, coimmunoprecipitation, and Western blotting demonstrated that YB-1 could form a protein complex with phosphorylated glycogen synthase kinase 3 beta (pGSK3β) to regulate Wnt/β-catenin. In mouse NAFLD livers, immunohistochemistry and Western blotting validated the finding of YB-1 gene downregulation leading to the inhibition of Wnt/β-catenin pathway activation, ultimately inhibiting lipid synthesis and reducing the inflammatory response. Similar to the in vitro investigation, β-catenin overexpression reversed such YB-1 downregulation-induced downstream effects. Upregulation of the YB-1 gene promoted the activation of the Wnt/β-catenin pathway, thus increasing lipid synthesis and the inflammatory response.However, downregulation of β-catenin reversed this phenomenon caused by upregulating YB-1.Conclusions: In summary, these results demonstrate that YB-1 regulates liver lipid metabolism by regulating the Wnt/β-catenin signaling pathway.

Quantitative proteomics of HFD-induced fatty liver uncovers novel transcription factors of lipid metabolism

“…However, the role of ILF2 in the regulation of lipid metabolism/NAFLD has not been reported. A recent study has demonstrated that YB-1, a ILF2 interacting protein, regulates liver lipid metabolism by regulating the Wnt/β-catenin signaling pathway 49 , which implied the possibility of ILF2 in the regulation of NAFLD. Thus, this study reports that ILF2 is a potential positive modulator of lipid metabolism by inhibiting fatty acid biosynthesis genes expression.…”

YBX-1 alleviates sepsis-stimulated lung epithelial cell injury

“…6 YBX-1 regulates gene transcription by binding to promoters with Y-box motifs. 7 Previous studies have found that YBX-1 is involved in tumor regulation. For example, overexpression of YBX-1 can promote the growth of pancreatic ductal adenocarcinoma and inhibit cell apoptosis by up-regulating of GSK3β axis.…”