Gut microbiota metabolite TMAO promoted lipid deposition and fibrosis process via KRT17 in fatty liver cells in vitro.

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide but still lacks specific treatment modalities. The gut microbiota and its metabolites have been shown to be intimately involved in NAFLD development, participating in and regulating disease progression. Trimethylamine N-oxide (TMAO), a metabolite highly dependent on the gut microbiota, has been shown to play deleterious regulatory roles in cardiovascular disease, but the relationship between it and NAFLD lacks validation from basic experiments. This research applied TMAO intervention by constructing fatty liver cell models in vitro to observe its effect on fatty liver cells and potential key genes and performed siRNA interference on the gene to verify the action. The results showed that TMAO intervention promoted the appearance of more red-stained lipid droplets in Oil-red O staining results, increased triglyceride (TG) levels and increased mRNA levels of liver fibrosis-related genes, and also identified one of the key genes, keratin17 (KRT17) via transcriptomics. Following the reduction in its expression level, under the same treatment, there were decreased red-stained lipid droplets, decreased TG levels, decreased indicators of impaired liver function as well as decreased mRNA levels of liver fibrosis-related genes. In conclusion, the gut microbiota metabolite TMAO could promote lipid deposition and fibrosis process via the KRT17 gene in fatty liver cells in vitro. • TMAO promotes lipid deposition in fatty liver cells in vitro. • TMAO promotes the fibrosis process of fatty liver cells in vitro. • KRT17 is the critical gene in the action of TMAO. • Reduced KRT17 expression levels diminish the cell-promoting effect of TMAO. [ABSTRACT FROM AUTHOR]