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Publication : Regulation of adipose tissue inflammation by interleukin 6.

First Author  Han MS Year  2020
Journal  Proc Natl Acad Sci U S A Volume  117
Issue  6 Pages  2751-2760
PubMed ID  31980524 Mgi Jnum  J:287981
Mgi Id  MGI:6391127 Doi  10.1073/pnas.1920004117
Citation  Han MS, et al. (2020) Regulation of adipose tissue inflammation by interleukin 6. Proc Natl Acad Sci U S A 117(6):2751-2760
abstractText  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 alpha. Collectively, these data demonstrate that the source of IL6 production plays a major role in the physiological regulation of metabolism.
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