Rabeprazole mitigates obesity-induced chronic inflammation and insulin resistance associated with increased M2-type macrophage polarization

Macrophage polarization is closely associated with obesity-induced chronic inflammation and Insulin resistance. Proton Pump Inhibitor Rabeprazole has long been used to treat gastritis and gastric ulcers. However, whether Rabeprazole plays a role in macrophage polarization during obesity is unknown. Here, we show that Rabeprazole suppresses M1-type macrophage-mediated inflammation, leads to increased M2-type macrophages and alters the polarization status from M1 to M2 in vitro. Mechanistically, Rabe-regulated macrophage polarization is associated with inhibition of NF-κB and activation of STAT6 signaling pathways. Furthermore, Rabeprazole induces M2-type adipose tissue macrophages and alleviates chronic inflammation, improving glucose tolerance and Insulin sensitivity in high-fat diet-fed mice. In addition, Rabeprazole increases CD206⁺ M2-type liver macrophages and relieves liver inflammation, alleviating liver injury and lipid accumulation. Thus, our findings show that Rabeprazole effectively regulates macrophage polarization and controls obesity-associated chronic inflammation and Insulin resistance, thus providing a potential therapeutic strategy against obesity-associated metabolic diseases.