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    Item type:Publication,
    Aloesin improves metabolic associated fatty liver disease and obesity by targeting TGFBR1
    (2026-04)
    Wu, Jianfeng
    ;
    Liu, Siqi
    ;
    Ma, Zhen
    ;
    ;
    Liao, Qichao
    BACKGROUND: Metabolic associated fatty liver disease (MAFLD) is a chronic liver condition with a high global prevalence. Obesity and its associated insulin resistance are among the main risk factors for MAFLD, for which no effective clinical treatments are currently available. Aloesin, a natural chromone compound derived from Aloe vera, has anti-inflammatory, antioxidant, anticancer, and antidiabetes activity. However, its involvement in MAFLD has not been systematically studied. PURPOSE: This study investigated the effectiveness of aloesin against MAFLD and obesity and elucidated its potential molecular mechanism. METHODS: Aloesin was added to the high-fat diet-of an induced mouse model and to oleic acid/palmitic acid-induced HepG2 cells to explore its effect on lipid metabolism. Molecular targets were identified by reverse docking, cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS). RESULTS: Aloesin significantly reduced lipid accumulation in hepatocytes in both the high-fat diet-induced MAFLD mouse model and the oleic acid/palmitic acid-induced HepG2 cells. It also alleviated oxidative stress and energy metabolism disorders and decreased the body fat mass in mice fed the high-fat diet, which ameliorated the pathological features of MAFLD and obesity. Target prediction and validation identified TGFBR1 as a direct target of aloesin, which was confirmed by CETSA and DARTS. Functional experiments demonstrated that overexpression of TGFBR1 increased lipid accumulation and metabolic disturbances, which were reversed by aloesin. CONCLUSION: Aloesin improved lipid deposition and slowed the progression of MAFLD by targeting TGFBR1. The results support its potential application for the prevention and treatment of MAFLD.