Regulation of adipose tissue inflammation by interleukin 6

Proc Natl Acad Sci U S A. 2020 Feb 11;117(6):2751-2760. doi: 10.1073/pnas.1920004117. Epub 2020 Jan 24.


Obesity is associated with a chronic state of low-grade inflammation and progressive tissue infiltration by immune cells and increased expression of inflammatory cytokines. It is established that interleukin 6 (IL6) regulates multiple aspects of metabolism, including glucose disposal, lipolysis, oxidative metabolism, and energy expenditure. IL6 is secreted by many tissues, but the role of individual cell types is unclear. We tested the role of specific cells using a mouse model with conditional expression of the Il6 gene. We found that IL6 derived from adipocytes increased, while IL6 derived from myeloid cells and muscle suppressed, macrophage infiltration of adipose tissue. These opposite actions were associated with a switch of IL6 signaling from a canonical mode (myeloid cells) to a noncanonical trans-signaling mode (adipocytes and muscle) with increased expression of the ADAM10/17 metalloprotease that promotes trans-signaling by the soluble IL6 receptor α. Collectively, these data demonstrate that the source of IL6 production plays a major role in the physiological regulation of metabolism.

Keywords: adipose tissue; inflammation; insulin resistance; interleukin 6.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM10 Protein / genetics
  • ADAM10 Protein / immunology
  • ADAM17 Protein / genetics
  • ADAM17 Protein / immunology
  • Adipocytes / immunology
  • Adipose Tissue / immunology*
  • Animals
  • Female
  • Humans
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology*
  • Macrophages / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle Cells / immunology
  • Myeloid Cells / immunology
  • Obesity / genetics
  • Obesity / immunology*
  • Species Specificity


  • Interleukin-6
  • ADAM10 Protein
  • ADAM17 Protein