Study on the mechanism of promoting NAFLD process by regulating glycolysis through PFKM in hypoxic microenvironment

NAFLD is a common disease but there is currently no specific drug available. One reason for this is that existing animal and cell models differ significantly from human models, while tissue-specific organoids have high consistency with human tissue structure and gene expression, making them a new model. Through the construction of a NAFLD based organoid model and proteomics, it was found that genes involved in the glycolysis pathway were significantly enriched. Among them, PFKM was significantly overexpressed in NAFLD tissues, and its function in NAFLD was validated in three models: cellular, organoid, and animal. Metabolomics studies showed that changes in PFKM led to significant changes in lactate levels and abnormal glucose absorption in the glycolysis pathway, suggesting that PFKM causes NAFLD through glycolysis.