Integrative transcriptomic and metabolomic analysis explores the mechanisms by which ACT001 treats MAFLD in mice.

Metabolic associated fatty liver disease (MAFLD) represents a significant public health concern. Previous studies have shown that ACT001 has therapeutic effects on MAFLD. This study investigated the potential mechanisms by which ACT001 may treat MAFLD through an integrated approach of transcriptomics and metabolomics. MAFLD model induced by high-fat diet was established, and ACT001 was given by gavage. Histological analysis was performed, and liver enzyme and lipid levels were measured. Transcriptomic analysis was performed to identify differentially expressed genes, while metabolomic analysis was used to detect differential metabolites. Pathways enriched by genes and metabolites affected by ACT001 were also identified. The differentially expressed genes were confirmed through RT-qPCR. ACT001 reduced the levels of liver enzymes and lipids, and alleviated pathological damage such as hepatic steatosis. The integration of transcriptomic and metabolomic analyses indicated that ACT001 may alleviate high-fat diet-induced MAFLD by regulating the linoleic acid and glutathione metabolic pathways. The validation of five differentially expressed genes using RT-qPCR yielded results that were consistent with the transcriptomics data. ACT001 may exert a therapeutic effect in MAFLD mice by modulating glutathione metabolism and linoleic acid metabolism. It has the potential to be a promising treatment for MAFLD.