Human umbilical cord mesenchymal stem cells ameliorate liver metabolism in diabetic rats with metabolic-associated fatty liver disease.

BACKGROUND: Diabetes mellitus (DM) and metabolic-associated fatty liver disease (MAFLD) are common metabolic disorders, and their coexistence can exacerbate the progression of either disease. Human umbilical cord mesenchymal stem cell (hUC-MSC) therapy has shown promising potential in the treatment of several metabolic diseases. AIM: To investigate how hUC-MSCs affect liver metabolism in diabetic rats with MAFLD and assess their therapeutic potential and underlying mechanisms. METHODS: A streptozotocin-induced rat model of DM with MAFLD was established, and hUC-MSCs were administered via tail vein injection. Changes in body weight, fasting blood glucose (FBG), and serum triglyceride (TG), alanine aminotransferase, aspartate aminotransferase levels, and pathological changes of liver were evaluated. Receiver operating characteristic analysis was used to assess the diagnostic value of differential metabolites and their ability to predict the therapeutic effects of hUC-MSCs. Spearman correlation was employed to analyze the relationships between liver metabolites and key biochemical markers. RESULTS: hUC-MSC treatment significantly reduced FBG and TG levels in diabetic rats with MAFLD and improved histological steatosis and injury in the liver. Metabolomic analysis indicated that hUC-MSCs significantly ameliorated liver metabolic disturbances via their regulatory effect on several key metabolic pathways related to carbohydrate, amino acid, and lipid metabolism. Receiver operating characteristic curve analysis revealed that 70 differential metabolites had good diagnostic value for DM with MAFLD and could effectively predict the therapeutic effect of hUC-MSCs. Moreover, Spearman correlation analysis confirmed that significant correlations existed between differential liver metabolites and the concentrations of biochemical markers (FBG, TG, alanine aminotransferase, aspartate aminotransferase). CONCLUSION: hUC-MSCs alleviate liver metabolic disturbances in diabetic rats with MAFLD, thereby mitigating the pathological state of DM and slowing the progression of MAFLD.