The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Regulation of adipose tissue inflammation by interleukin 6
Open accessAbstract
Significance 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.
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In the citing paper
“Additionally, fibroblast growth factor 21 (FGF21) is also upregulated by physical activity and may act downstream of these signals to further enhance the thermogenic program [53].”
From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [53]
Experimental — accuracy not yet measuredIn the citing paper
“The finding of opposite actions of IL-6, depending of the cell source, appeared to be due to a switch of IL6 signaling from a canonical mode (myeloid cells) to a noncanonical trans-signaling mode (adipocytes and muscle) which involved increased expression of the ADAM10/17 metalloprotease that enhances trans-signaling via the soluble IL6 receptor α (215).”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [215]
In the citing paper
“Using a mouse model with conditional expression of the Il6 gene, it was found that IL6 derived from adipocytes increased, while IL6 derived from myeloid cells and muscle suppressed, macrophage infiltration of adipose tissue.”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [215]
In the citing paper
“A recent murine study suggested that IL-6 may induce either pro- or anti-inflammatory actions depending on cell source (215).”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [215]
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Citations
Cites
The pro- and anti-inflammatory properties of the cytokine interleukin-6
Scheller, J., Chalaris, A., Schmidt-Arras, D., & Rose-John, S. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2011.01.034 · Cited by 3,212
Conditional gene targeting in macrophages and granulocytes using LysMcre mice
Clausen, B. E., Burkhardt, C., Reith, W., Renkawitz, R., & Förster, I. (1999) · Transgenic Research · doi:10.1023/a:1008942828960 · Cited by 2,098
Subcutaneous Adipose Tissue Releases Interleukin-6, But Not Tumor Necrosis Factor-α,in Vivo1
Mohamed‐Ali, V., Goodrick, S., Rawesh, A., Katz, D. R., Miles, J. M., Yudkin, J. S., Klein, S., & Coppack, S. W. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.12.4450 · Cited by 2,032
Ellingsgaard, H., Hauselmann, I., Schuler, B., Habib, A. M., Baggio, L. L., Meier, D. T., Eppler, E., Bouzakri, K., Wueest, S., Muller, Y. D., et al. (2011) · Nature Medicine · doi:10.1038/nm.2513 · Cited by 922
Carey, A. L., Steinberg, G. R., Macaulay, S. L., Thomas, W. G., Holmes, A. G., Ramm, G., Prelovsek, O., Hohnen-Behrens, C., Watt, M. J., James, D. E., et al. (2006) · Diabetes · doi:10.2337/db05-1404 · Cited by 898
IL-6 pathway in the liver: From physiopathology to therapy
Schmidt-Arras, D., & Rose-John, S. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.02.004 · Cited by 881 · cited 1×
“The physiology of IL6 signaling is complex because the effects of IL6 on metabolism requires signal integration between cell types (4) that involve proinflammatory, anti-inflammatory, and noninflammatory mechanisms (5).”
BackgroundInterleukin-6 in acute exercise and training: what is the biological relevance?
Fischer, C. P. (2026) · PubMed · doi:10.22029/eir.2006.1620 · Cited by 817
Interleukin-6 stimulates lipolysis and fat oxidation in humans
van Hall, G., Steensberg, A., Sacchetti, M., Fischer, C., Keller, C., Schjerling, P., Hiscock, N., Møller, K., Saltin, B., Febbraio, M. A., et al. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021687 · Cited by 767
Mauer, J., Chaurasia, B., Goldau, J., Vogt, M. C., Ruud, J., Nguyen, K. D., Theurich, S., Hausen, A. C., Schmitz, J., Brönneke, H. S., et al. (2014) · Nature Immunology · doi:10.1038/ni.2865 · Cited by 727
Perry, R. J., Camporez, J.-P. G., Kursawe, R., Titchenell, P. M., Zhang, D., Perry, C. J., Jurczak, M. J., Abudukadier, A., Han, M. S., Zhang, X.-M., et al. (2015) · Cell · doi:10.1016/j.cell.2015.01.012 · Cited by 719
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Muscle–Organ Crosstalk: The Emerging Roles of Myokines
Severinsen, M. C. K., & Pedersen, B. K. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnaa016 · Cited by 1,226
“The finding of opposite actions of IL-6, depending of the cell source, appeared to be due to a switch of IL6 signaling from a canonical mode (myeloid cells) to a noncanonical trans-signaling mode (adipocytes and muscle) which involved increased expression of the ADAM10/17 metalloprotease that enhances transsignaling v…”
BackgroundInflammation and Skeletal Muscle Wasting During Cachexia
Webster, J. M., Kempen, L. J. A. P., Hardy, R. S., & Langen, R. C. J. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.597675 · Cited by 372
The complex role of adipokines in obesity, inflammation, and autoimmunity
Taylor, E. B. (2021) · Clinical Science · doi:10.1042/cs20200895 · Cited by 369
Interleukin 6 as an Energy Allocator in Muscle Tissue
Kistner, T. M., Pedersen, B. K., & Lieberman, D. E. (2022) · Nature Metabolism · doi:10.1038/s42255-022-00538-4 · Cited by 295
Pathogenesis and treatment of non-alcoholic steatohepatitis and its fibrosis
Lee, K., Wu, P.-S., & Lin, H. (2022) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2022.0237 · Cited by 269
Metadata
- Authors
- Han, M. S., White, A., Perry, R. J., Camporez, J.-P., Hidalgo, J., Shulman, G. I., & Davis, R. J.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- Yale University (US)
- Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06520;
- Universitat Autònoma de Barcelona (ES)
- Corresponding author
- Davis, Roger J.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2020-01-24
- Volume
- 117
- Issue
- 6
- Pages
- 2751-2760
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC7022151
- OpenAlex
- W3002801990
- Cited by
- 344
- References
- 37
- Citations by year
- 2026: 37 · 2025: 40 · 2024: 53 · 2023: 59 · 2022: 64 · 2021: 57 · 2020: 31
- FWCI
- 37.78
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- eScholarship@UMassChan (submittedVersion, cc-by-nc-nd)
- Dipòsit Digital de Documents de la UAB (Universitat Autònoma de Barcelona) (submittedVersion, cc-by-nc-nd)
- Funders
- American Heart Association (19CDA34660270)
- Ministerio de Economía y Competitividad (SAF2014-56546-R, RTI2018-101105-B-I00)
- HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK107220, R01 DK112698, R01 DK121545, R01 DK116774, R01 DK114793, P30 DK045735)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Keywords
- interleukin-6, adipose tissue inflammation, low-grade inflammation, metabolic syndrome, adipose tissue macrophages, myeloid cells, adipocytes, skeletal muscle, macrophage accumulation, immune cell infiltration
- MeSH terms
- ADAM10 Protein, ADAM17 Protein, Adipose Tissue, Animals, Female, Humans, Macrophages, Male, Mice, Inbred C57BL, Obesity, Species Specificity, Interleukin-6, Adipocytes, Myeloid Cells, Muscle Cells, Mice
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