Hepcidin gene silencing ameliorated inflammation and insulin resistance in adipose tissue of db/db mice via inhibiting METs formation

Mol Immunol. 2021 May:133:110-121. doi: 10.1016/j.molimm.2021.02.015. Epub 2021 Feb 25.

Abstract

As a major feature of diabetes, inflammation is closely related to macrophage extracellular traps and the expression of hepcidin upregulated by diabetes is reportedly involved in chronic inflammation. Therefore, we aimed to explore whether hepcidin could be implicated in inflammation and macrophage extracellular traps (METs) formation. The diabetic db/db mouse model was established exhibiting insulin resistance (IR), inflammation, macrophages infiltration and higher expression of hepcidin, where samples were obtained from epididymal adipose tissue. We observed that inflammation and IR improved in adipose tissue of mice treated with hepcidin gene silencing. Furthermore, METs formation could be markedly inhibited via hepcidin gene silencing followed by attenuated inflammatory response due to METs, indicating hepcidin gene silencing played a key role in anti-inflammation by inhibiting METs formation. So, we concluded that hepcidin gene silencing has a potential for treatment of diabetes due to its ability to ameliorate inflammation via inhibiting METs formation.

Keywords: Hepcidin; Inflammation; Insulin resistance; Macrophage extracellular traps.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Diabetes Mellitus / genetics
  • Diabetes Mellitus / pathology
  • Diabetes Mellitus / therapy*
  • Extracellular Traps / immunology*
  • Hepcidins / genetics*
  • Inflammation / genetics
  • Inflammation / immunology
  • Insulin Resistance / genetics
  • Insulin Resistance / physiology
  • Macrophages / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Oxidative Stress / physiology
  • RAW 264.7 Cells
  • RNA Interference*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / therapeutic use*

Substances

  • Hepcidins
  • RNA, Small Interfering