Regulation of adipose tissue inflammation by interleukin 6
Han, Myoung Sook (University of Massachusetts Medical School)
White, Alexis (University of Massachusetts Medical School)
Perry, Rachel J. (Yale School of Medicine)
Camporez, Joao-Paulo (Yale School of Medicine)
Hidalgo Pareja, Juan (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Shulman, Gerald I. (Yale School of Medicine)
Davis, Roger (University of Massachusetts Medical School)

Data:	2020
Resum:	Chronic low-grade inflammation is a key driver of metabolic syndrome. This inflammatory response is mediated by immune-cell infiltration and the expression of inflammatory cytokines. IL6 is implicated in this response, but the physiological role of IL6 signaling is unclear. Here, we demonstrate that the source of IL6 influences the nature of the inflammatory response. We report that IL6 secreted by myeloid cells inhibits adipose tissue macrophage (ATM) accumulation by a canonical signaling mechanism, but IL6 secreted by adipocytes or muscle promotes ATM accumulation by a noncanonical mechanism. These observations provide physiological insight into the complexity of IL6-mediated regulation of inflammation. 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.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Adipose tissue ; Inflammation ; Interleukin 6 ; Insulin resistance
Publicat a:	Proceedings of the National Academy of Sciences of the United States of America, Vol. 117 (january 2020) , p. 2751-2760, ISSN 1091-6490

DOI: 10.1073/pnas.1920004117
PMID: 31980524

10 p, 2.2 MB

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