UMMS Affiliation

Program in Molecular Medicine; Davis Lab

Publication Date

2020-02-11

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Biochemical Phenomena, Metabolism, and Nutrition | Cell Biology | Cellular and Molecular Physiology | Endocrinology, Diabetes, and Metabolism | Hemic and Immune Systems | Nutritional and Metabolic Diseases

Abstract

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.

Keywords

adipose tissue, inflammation, insulin resistance, interleukin 6

Rights and Permissions

Copyright © 2020 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).

DOI of Published Version

10.1073/pnas.1920004117

Source

Han MS, White A, Perry RJ, Camporez JP, Hidalgo J, Shulman GI, Davis RJ. 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. PMID: 31980524; PMCID: PMC7022151. Link to article on publisher's site

Journal/Book/Conference Title

Proceedings of the National Academy of Sciences of the United States of America

Related Resources

Link to Article in PubMed

PubMed ID

31980524

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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