Rebamipide treatment ameliorates obesity phenotype by regulation of immune cells and adipocytes

PLoS One. 2022 Dec 27;17(12):e0277692. doi: 10.1371/journal.pone.0277692. eCollection 2022.

Abstract

Obesity is a medical term used to describe an over-accumulation of adipose tissue. It causes abnormal physiological and pathological processes in the body. Obesity is associated with systemic inflammation and abnormalities in immune cell function. Rebamipide, an amino acid derivative of 2-(1H)-quinolinone, has been used as a therapeutic for the protection from mucosal damage. Our previous studies have demonstrated that rebamipide treatment regulates lipid metabolism and inflammation, leading to prevention of weight gain in high-fat diet mice. In this study, mice were put on a high calorie diet for 11 weeks while receiving injections of rebamipide. Rebamipide treatment reduced the body weight, liver weight and blood glucose levels compared to control mice and reduced both glucose and insulin resistance. Fat accumulation has been shown to cause pro-inflammatory activity in mice. Treatment with rebamipide decreased the prevalence of inflammatory cells such as Th2, Th17 and M1 macrophages and increased anti-inflammatory Treg and M2 macrophages in epididymal fat tissue. Additionally, rebamipide addition inhibited adipocyte differentiation in 3T3-L1 cell lines. Taken together, our study demonstrates that rebamipide treatment is a novel and effective method to prevent diet-induced obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / metabolism
  • Adipose Tissue / metabolism
  • Animals
  • Diet, High-Fat / adverse effects
  • Inflammation / metabolism
  • Insulin Resistance*
  • Mice
  • Mice, Inbred C57BL
  • Obesity / complications
  • Phenotype
  • Quinolones* / metabolism
  • Quinolones* / pharmacology
  • Quinolones* / therapeutic use

Substances

  • rebamipide
  • Quinolones

Associated data

  • figshare/10.6084/m9.figshare.21638276.v1

Grants and funding

This research was supported by the Institute of Clinical Medicine Research of Bucheon St. Mary’s Hospital, Research Fund (grant number BCMC20AC04), Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (grant number 2020R1I1A1A01072520), (grant number 2021R1F1A1056064) and (grant number 2020R1I1A1A01072547). The funders had roles in study design, data collection and analysis of the manuscript.