Construction of an FSH induced liver organoid model for investigating lipid metabolism abnormalities and study of the regulatory role of key lncRNAs

The health problems of the elderly, especially the elderly women, are increasingly concerned. The prevalence of abnormal liver lipid metabolism in women after menopause is increasing, which is highly related to estrogen and follicle stimulating hormone. However, hormone replacement therapy is highly controversial, and will bring risks such as breast cancer and coronary heart disease. Therefore, this study aims to build an effective and convenient in vitro disease model and perform functional verification to analyze the molecular mechanism of candidate lncRNAs participating in FSH-induced liver lipid metabolism. The results indicated the successful preliminary establishment of an in vitro model for FSH-induced lipid metabolism abnormalities. High-throughput sequencing and bioinformatics analysis revealed a total of 174 differentially expressed lncRNAs. Utilizing a comprehensive database, we screened five candidate lncRNAs and conducted interference tests specifically on the upregulated lncRNA ENSMUST00000244884. The findings demonstrated that knocking down this lncRNA led to an increase in the expression of the LXR and ACOX1 genes, which are crucial for lipid metabolism. Consequently, the lipid metabolism abnormality phenotype was alleviated. Based on the experimental results, we have determined that bile-derived liver organoids are well-suited for constructing an in vitro disease model of hormone-induced lipid metabolism abnormalities, enabling effective observation of lipid phenotypes. Furthermore, we have screened and identified lncRNAs involved in hormone-regulated lipid metabolism abnormalities at the non-coding regulatory level. These findings offer potential diagnostic markers and therapeutic targets for disorders related to lipid metabolism. • Bile-derived liver organoids are well-suited for constructing an in vitro disease model of hormone-induced lipid metabolism abnormalities, enabling effective observation of lipid phenotypes. • High-throughput sequencing and bioinformatics analysis revealed a total of 174 differentially expressed lncRNAs involved in hormone-regulated lipid metabolism abnormalities at the non-coding regulatory level. • Knocking down the upregulated lncRNA ENSMUST00000244884 led to an increase in the expression of the LXR and ACOX1 genes, offering potential diagnostic markers and therapeutic targets for disorders related to lipid metabolism.