2. Academic Validation
  3. Rabeprazole mitigates obesity-induced chronic inflammation and insulin resistance associated with increased M2-type macrophage polarization

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

  • Biochim Biophys Acta Mol Basis Dis. 2024 Mar 31;1870(5):167142. doi: 10.1016/j.bbadis.2024.167142.
Yunfang Li 1,  Jiayue Hao 2,  Xianghui Kong 3,  Weiyi Yuan 2,  Yingying Shen 4,  Zhaoyuan Hui 5,  Xinliang Lu 6
Affiliations

Affiliations

  • 1 Hangzhou Children's Hospital, 310014 Hangzhou, China.
  • 2 Institute of Immunology, Zhejiang University School of Medicine, 310009 Hangzhou, China.
  • 3 Institute of Immunology and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, 310058 Hangzhou, China.
  • 4 Laboratory of Cancer Biology, Key lab of Biotherapy in Zhejiang, Cancer Center of Zhejiang University, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, Zhejiang 310020, China.
  • 5 Yulin Hospital, The First Affiliated Hospital of Xi'an Jiaotong University, Yulin, Shanxi 719000, China. Electronic address: huizhaoyuan@163.com.
  • 6 Institute of Immunology and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, 310058 Hangzhou, China. Electronic address: xllu@zju.edu.cn.
PMID: 38565384 DOI: 10.1016/j.bbadis.2024.167142
Abstract

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.

Keywords

Chronic inflammation; Insulin resistance; Macrophage polarization; Rabeprazole.

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