Chaihu-Wendan Decoction alleviates obesity through PTEN-mediated uncoupling of metabolic signaling and macrophage activation

Objective: Obesity is increasingly recognized as an immunometabolic disorder driven by dysregulated crosstalk between visceral adipose tissue and the liver, particularly along the liver-omentum axis, which promotes insulin resistance and hepatic steatosis. Although Chaihu-Wendan Decoction (CHWD) is effective for metabolic disorders, its molecular mechanisms of action on this inflammatory axis remains unclear. This study aimed to investigate the therapeutic mechanisms of CHWD in high-fat diet (HFD)-induced obesity model, specifically focusing on insulin signaling and immune microenvironment remodeling in the liver-omentum axis. Method: C57BL/6J mice were fed a HFD to induce obesity and treated with CHWD. Metabolic phenotypes were assessed via biochemical and histological analyses. The molecular mechanisms were explored by evaluating the PTEN/PI3K/AKT/mTOR pathway and omental macrophage profiles using Western blot, ELISA, and immunohistochemistry. Results: macrophage population accompanied by suppression of iNOS-mediated cytotoxic effector functions. Conclusion: CHWD alleviates HFD-induced obesity and metabolic inflammation by coordinately targeting the PTEN/AKT/mTOR axis and reprogramming omental immunity. These findings provide the primary evidence supporting that CHWD modulates the liver-omentum axis via distinct signaling and immune mechanisms, offering a novel therapeutic strategy for metabolic syndrome.