Cited by 344Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismCytokine Signaling Pathways and Interactions

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Regulation of adipose tissue inflammation by interleukin 6

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Han, Myoung Sook, White, Alexis, Perry, Rachel J., Camporez, Joao-Paulo, Hidalgo, Juan, Shulman, Gerald I., Davis, Roger J.·2020·Proceedings of the National Academy of Sciences

Abstract

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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Fig. 1. The HFD induced infiltration of macrophages and secretion of cytokines. (A and B) The SVF of gWAT was isolated from HFD-fed (0, 4, and 16 wk) mice and examined by flow cytometry to detect the total number of F4/80+ ATMs, the number of F4/80+ CD11c+ CD206− (M1-like) ATMs, and the number of F4/80+ CD11c− CD206+ (M2-like) ATMs per mouse (mean ± SEM; n = 2). *P < 0.05; **P < 0.01; ***P < 0.001. (C) Total RNA was isolated from ADF and SVF from HFD-fed (0, 4, and 16 wk) mice. The relative expression of mRNA associated with makers of macrophages (Adgre1), M1-polarized macrophages (Ccl2, Ccl5, Il6, and Tnfα), and adipocytes (Adipoq) was measured by qRT-PCR assays (mean ± SEM; n = 4 ∼ 6). *P < 0.05; **P < 0.01; ***P < 0.001. (D) Total RNA was isolated from gWAT and BAT from CD- and HFD-fed ADWT and ADΔIL6 mice. The relative expression of Il6 mRNA was measured by qRT-PCR assays (mean ± SEM; n = 5 ∼ 8). *P < 0.05; **P < 0.01. (E) Total RNA was isolated from gWAT and BAT in CD- and HFD-fed ФWT and ФΔIL6 mice. The relative expression of Il6 mRNA was measured by qRT-PCR assays (mean ± SEM; n = 4 ∼ 8). *P < 0.05; ***P < 0.001.
Fig. 1. The HFD induced infiltration of macrophages and secretion of cytokines. (A and B) The SVF of gWAT was isolated from HFD-fed (0, 4, and 16 wk) mice and examined by flow cytometry to detect the total number of F4/80+ ATMs, the number of F4/80+ CD11c+ CD206− (M1-like) ATMs, and the number of F4/80+ CD11c− CD206+ (M2-like) ATMs per mouse (mean ± SEM; n = 2). *P < 0.05; **P < 0.01; ***P < 0.001. (C) Total RNA was isolated from ADF and SVF from HFD-fed (0, 4, and 16 wk) mice. The relative expression of mRNA associated with makers of macrophages (Adgre1), M1-polarized macrophages (Ccl2, Ccl5, Il6, and Tnfα), and adipocytes (Adipoq) was measured by qRT-PCR assays (mean ± SEM; n = 4 ∼ 6). *P < 0.05; **P < 0.01; ***P < 0.001. (D) Total RNA was isolated from gWAT and BAT from CD- and HFD-fed ADWT and ADΔIL6 mice. The relative expression of Il6 mRNA was measured by qRT-PCR assays (mean ± SEM; n = 5 ∼ 8). *P < 0.05; **P < 0.01. (E) Total RNA was isolated from gWAT and BAT in CD- and HFD-fed ФWT and ФΔIL6 mice. The relative expression of Il6 mRNA was measured by qRT-PCR assays (mean ± SEM; n = 4 ∼ 8). *P < 0.05; ***P < 0.001.CC BY-NC-ND · PubMed Central
Fig. 2. Adipocyte IL6 promotes obesity-induced insulin resistance. (A) The change in body mass of CD- and HFD-fed ADWT and ADΔIL6 mice is presented (mean ± SEM; n = 7 ∼ 14). (B) Body composition was examined by proton magnetic resonance spectroscopy (mean ± SEM; n = 7 ∼ 8). (C) The blood concentration of glucose in overnight fasted mice and the blood glucose concentration in fed mice were measured (mean ± SEM; n = 7 ∼ 14). **P < 0.01. (D) The CD- and HFD-fed (16 wk.) mice were examined by GTTs (mean ± SEM; n = 7 ∼ 14). *P < 0.05; **P < 0.01. (E) The CD- and HFD-fed (16 wk) mice were examined by ITTs (mean ± SEM; n = 5 ∼ 13). *P < 0.05; **P < 0.01. (F) GIR measurements were performed by i.p. injection of glucose (mean ± SEM; n = 6 ∼ 7). *P < 0.05. (G–I) The CD- and HFD-fed mice (16 wk) were fasted overnight, treated by i.p. injection with 1 U/kg insulin (15 min), and examined by immunoblot analysis of gWAT, liver, and gastrocnemius muscle by probing with antibodies to phospho-Akt (pThr308 and pSer473), Akt, and αTubulin. Relative quantitation of the phospho-Akt immunoblots is presented below each subpanel.
Fig. 2. Adipocyte IL6 promotes obesity-induced insulin resistance. (A) The change in body mass of CD- and HFD-fed ADWT and ADΔIL6 mice is presented (mean ± SEM; n = 7 ∼ 14). (B) Body composition was examined by proton magnetic resonance spectroscopy (mean ± SEM; n = 7 ∼ 8). (C) The blood concentration of glucose in overnight fasted mice and the blood glucose concentration in fed mice were measured (mean ± SEM; n = 7 ∼ 14). **P < 0.01. (D) The CD- and HFD-fed (16 wk.) mice were examined by GTTs (mean ± SEM; n = 7 ∼ 14). *P < 0.05; **P < 0.01. (E) The CD- and HFD-fed (16 wk) mice were examined by ITTs (mean ± SEM; n = 5 ∼ 13). *P < 0.05; **P < 0.01. (F) GIR measurements were performed by i.p. injection of glucose (mean ± SEM; n = 6 ∼ 7). *P < 0.05. (G–I) The CD- and HFD-fed mice (16 wk) were fasted overnight, treated by i.p. injection with 1 U/kg insulin (15 min), and examined by immunoblot analysis of gWAT, liver, and gastrocnemius muscle by probing with antibodies to phospho-Akt (pThr308 and pSer473), Akt, and αTubulin. Relative quantitation of the phospho-Akt immunoblots is presented below each subpanel.CC BY-NC-ND · PubMed Central
Fig. 3. Adipocyte IL6 promotes M1 polarization and an infiltration of ATMs. (A) ADWT and ADΔIL6 mice were fed a CD or a HFD for 16 wk. (A, Left) Sections of gWAT were stained with hematoxylin and eosin. (Scale bar, 100 µm.) (A, Center) Macrophages were stained by using an antibody to F4/80 (green), and nuclei were stained by using DAPI (blue) detection by fluorescence microscopy. (Scale bar, 50 µm.) (A, Right) ATMs were quantitated by measurement of F4/80 staining of tissue section using ImageJ software (mean ± SEM; n = 9 ∼ 15). **P < 0.01. (B) The SVF of gWAT was isolated from CD- and HFD-fed (16 wk) mice and examined by flow cytometry to detect the total number of ATMs (F4/80+), the number of M1-like ATMs (F4/80+ CD11c+ CD206−), and the number of M2-like ATMs (F4/80+ CD11c− CD206+) (mean ± SEM; n = 4). *P < 0.05; **P < 0.01. (C) Total RNA was isolated from gWAT from CD- and HFD-fed ADWT and ADΔIL6 mice. The relative expression of mRNA associated with markers of macrophages (Adgre1 and Cd68), M1-like polarized macrophages (Ccl2, Cd11c, and Tnfα), and M2-like polarized macrophages (Arg1, Mgl1, Mgl2, Mrc1, and Mrc2) was measured by qRT-PCR assays (mean ± SEM; n = 6 ∼ 8). *P < 0.05; **P < 0.01. (D and E) Total RNA was isolated from gWAT from CD- and HFD-fed ADWT and ADΔIL6 mice. The relative expression of the eosinophil marker (Ccr3) and T cell markers (Cd4, Cd8, and Foxp3) were measured by qRT-PCR assays of mRNA (mean ± SEM; n = 6 ∼ 8). *P < 0.05. (F) The relative expression of the receptor Ccr2 and the ligands Ccl2, Ccl7, and Ccl8; and the receptor Ccr5 and the ligands Ccl3, Ccl4, Ccl5, and Ccl8 was measured by qRT-PCR assays of mRNA (mean ± SEM; n = 6 ∼ 8). *P < 0.05; **P < 0.01.
Fig. 3. Adipocyte IL6 promotes M1 polarization and an infiltration of ATMs. (A) ADWT and ADΔIL6 mice were fed a CD or a HFD for 16 wk. (A, Left) Sections of gWAT were stained with hematoxylin and eosin. (Scale bar, 100 µm.) (A, Center) Macrophages were stained by using an antibody to F4/80 (green), and nuclei were stained by using DAPI (blue) detection by fluorescence microscopy. (Scale bar, 50 µm.) (A, Right) ATMs were quantitated by measurement of F4/80 staining of tissue section using ImageJ software (mean ± SEM; n = 9 ∼ 15). **P < 0.01. (B) The SVF of gWAT was isolated from CD- and HFD-fed (16 wk) mice and examined by flow cytometry to detect the total number of ATMs (F4/80+), the number of M1-like ATMs (F4/80+ CD11c+ CD206−), and the number of M2-like ATMs (F4/80+ CD11c− CD206+) (mean ± SEM; n = 4). *P < 0.05; **P < 0.01. (C) Total RNA was isolated from gWAT from CD- and HFD-fed ADWT and ADΔIL6 mice. The relative expression of mRNA associated with markers of macrophages (Adgre1 and Cd68), M1-like polarized macrophages (Ccl2, Cd11c, and Tnfα), and M2-like polarized macrophages (Arg1, Mgl1, Mgl2, Mrc1, and Mrc2) was measured by qRT-PCR assays (mean ± SEM; n = 6 ∼ 8). *P < 0.05; **P < 0.01. (D and E) Total RNA was isolated from gWAT from CD- and HFD-fed ADWT and ADΔIL6 mice. The relative expression of the eosinophil marker (Ccr3) and T cell markers (Cd4, Cd8, and Foxp3) were measured by qRT-PCR assays of mRNA (mean ± SEM; n = 6 ∼ 8). *P < 0.05. (F) The relative expression of the receptor Ccr2 and the ligands Ccl2, Ccl7, and Ccl8; and the receptor Ccr5 and the ligands Ccl3, Ccl4, Ccl5, and Ccl8 was measured by qRT-PCR assays of mRNA (mean ± SEM; n = 6 ∼ 8). *P < 0.05; **P < 0.01.CC BY-NC-ND · PubMed Central
Fig. 4. Myeloid-cell IL6 increases energy expenditure. Metabolic cage analysis of CD- and HFD-fed ФWT and ФΔIL6 mice (6 wk) to measure oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory exchange rate (RER), energy expenditure (EE), and activity (A and B) and food intake per mouse (C) is presented (mean ± SEM; n = 8). **P < 0.01; ***P < 0.001.
Fig. 4. Myeloid-cell IL6 increases energy expenditure. Metabolic cage analysis of CD- and HFD-fed ФWT and ФΔIL6 mice (6 wk) to measure oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory exchange rate (RER), energy expenditure (EE), and activity (A and B) and food intake per mouse (C) is presented (mean ± SEM; n = 8). **P < 0.01; ***P < 0.001.CC BY-NC-ND · PubMed Central
Fig. 5. Macrophage IL6 suppresses diet-induced insulin resistance. (A) The change in body mass of CD- and HFD-fed ФWT and ФΔIL6 mice is presented (mean ± SEM; n = 6 ∼ 8). *P < 0.05; **P < 0.01; ***P < 0.001. (B) Body composition was examined by proton magnetic resonance spectroscopy (mean ± SEM; n = 6 ∼ 8). *P < 0.05; **P < 0.01. (C) The blood concentration of glucose in overnight fasted mice and fed mice was measured (mean ± SEM; n = 6 ∼ 8). **P < 0.01. (D) CD- and HFD-fed (16 wk) mice were examined by GTTs (mean ± SEM; n = 5 ∼ 8). *P < 0.05; **P < 0.01). (E) CD- and HFD-fed (16 wk) mice were examined by ITTs (mean ± SEM; n = 5 ∼ 8). *P < 0.05; **P < 0.01. (F) CD- and HFD-fed (16 wk) mice were examined by GIR (mean ± SEM; n = 5 ∼ 7). (G) Hyperinsulinemic–euglycemic clamps of CD- and HFD-fed (8 wk) mice were used to measure the glucose infusion rate, whole-body glucose uptake, EGP, NEFA suppression, whole-body glycerol turnover, whole-body palmitate turnover, and glucose uptake in gWAT, subcutaneous WAT (scWAT), and gastrocnemius muscle (mean ± SEM; n = 3 ∼ 6). *P < 0.05; **P < 0.01.
Fig. 5. Macrophage IL6 suppresses diet-induced insulin resistance. (A) The change in body mass of CD- and HFD-fed ФWT and ФΔIL6 mice is presented (mean ± SEM; n = 6 ∼ 8). *P < 0.05; **P < 0.01; ***P < 0.001. (B) Body composition was examined by proton magnetic resonance spectroscopy (mean ± SEM; n = 6 ∼ 8). *P < 0.05; **P < 0.01. (C) The blood concentration of glucose in overnight fasted mice and fed mice was measured (mean ± SEM; n = 6 ∼ 8). **P < 0.01. (D) CD- and HFD-fed (16 wk) mice were examined by GTTs (mean ± SEM; n = 5 ∼ 8). *P < 0.05; **P < 0.01). (E) CD- and HFD-fed (16 wk) mice were examined by ITTs (mean ± SEM; n = 5 ∼ 8). *P < 0.05; **P < 0.01. (F) CD- and HFD-fed (16 wk) mice were examined by GIR (mean ± SEM; n = 5 ∼ 7). (G) Hyperinsulinemic–euglycemic clamps of CD- and HFD-fed (8 wk) mice were used to measure the glucose infusion rate, whole-body glucose uptake, EGP, NEFA suppression, whole-body glycerol turnover, whole-body palmitate turnover, and glucose uptake in gWAT, subcutaneous WAT (scWAT), and gastrocnemius muscle (mean ± SEM; n = 3 ∼ 6). *P < 0.05; **P < 0.01.CC BY-NC-ND · PubMed Central
Fig. 6. Macrophage IL6 suppresses the accumulation and M1-like polarization of ATMs. (A, Left) CD- and HFD-fed (16 wk) ФWT and ФΔIL6 mice were examined by staining sections of gWAT with hematoxylin and eosin. (Scale bar, 100 µm.) (A, Center) Macrophages were stained by using an antibody to F4/80 and detection by fluorescence microscopy. (Scale bar, 50 µm.) (A, Right) ATMs were quantitated by measurement of F4/80 staining of tissue sections using ImageJ software (mean ± SEM; n = 8 ∼ 11). ***P < 0.001. (B) The SVF of gWAT was isolated from ФWT and ФΔIL6 CD- and HFD-fed (16 wk) mice and examined by flow cytometry to detect the total number of ATMs (F4/80+), M1-like ATMs (F4/80+ CD11c+ CD206−), and M2-like ATMs (F4/80+ CD11c− CD206+) (mean ± SEM; n = 5). *P < 0.05. (C) Total RNA was isolated from gWAT of CD- and HFD-fed ФWT and ФΔIL6 mice (16 wk). The relative expression of mRNA associated with macrophages (Adgre1 and Cd68), M1-like polarized macrophages (Ccl2, Cd11c, and Tnfα), and M2-like polarized macrophages (Arg1, Mgl1, Mgl2, Mrc1, and Mrc2) was measured by qRT-PCR assays (mean ± SEM; n = 5 ∼ 8). *P < 0.05; **P < 0.01; ***P < 0.001. (D and E) The relative expression of the eosinophil marker (Ccr3), neutrophil marker (Mpo), and T cell markers (Cd4, Cd8, and Foxp3) were measured by qRT-PCR assays of mRNA (mean ± SEM; n = 5 ∼ 8). *P < 0.05, ***P < 0.001. (F) The relative expression of the receptor Ccr2 (and ligands Ccl2, Ccl7, and Ccl8) and the receptor Ccr5 (and ligands Ccl3, Ccl4, Ccl5, and Ccl8) were measured by qRT-PCR assays of mRNA (mean ± SEM; n = 5 ∼ 8). *P < 0.05; **P < 0.01.
Fig. 6. Macrophage IL6 suppresses the accumulation and M1-like polarization of ATMs. (A, Left) CD- and HFD-fed (16 wk) ФWT and ФΔIL6 mice were examined by staining sections of gWAT with hematoxylin and eosin. (Scale bar, 100 µm.) (A, Center) Macrophages were stained by using an antibody to F4/80 and detection by fluorescence microscopy. (Scale bar, 50 µm.) (A, Right) ATMs were quantitated by measurement of F4/80 staining of tissue sections using ImageJ software (mean ± SEM; n = 8 ∼ 11). ***P < 0.001. (B) The SVF of gWAT was isolated from ФWT and ФΔIL6 CD- and HFD-fed (16 wk) mice and examined by flow cytometry to detect the total number of ATMs (F4/80+), M1-like ATMs (F4/80+ CD11c+ CD206−), and M2-like ATMs (F4/80+ CD11c− CD206+) (mean ± SEM; n = 5). *P < 0.05. (C) Total RNA was isolated from gWAT of CD- and HFD-fed ФWT and ФΔIL6 mice (16 wk). The relative expression of mRNA associated with macrophages (Adgre1 and Cd68), M1-like polarized macrophages (Ccl2, Cd11c, and Tnfα), and M2-like polarized macrophages (Arg1, Mgl1, Mgl2, Mrc1, and Mrc2) was measured by qRT-PCR assays (mean ± SEM; n = 5 ∼ 8). *P < 0.05; **P < 0.01; ***P < 0.001. (D and E) The relative expression of the eosinophil marker (Ccr3), neutrophil marker (Mpo), and T cell markers (Cd4, Cd8, and Foxp3) were measured by qRT-PCR assays of mRNA (mean ± SEM; n = 5 ∼ 8). *P < 0.05, ***P < 0.001. (F) The relative expression of the receptor Ccr2 (and ligands Ccl2, Ccl7, and Ccl8) and the receptor Ccr5 (and ligands Ccl3, Ccl4, Ccl5, and Ccl8) were measured by qRT-PCR assays of mRNA (mean ± SEM; n = 5 ∼ 8). *P < 0.05; **P < 0.01.CC BY-NC-ND · PubMed Central
Fig. 7. Muscle IL6 suppresses the accumulation and M1-like polarization of ATMs. (A) The concentration of circulating IL6 in blood was measured from exercised CD- or HFD-fed (16 wk) MWT and MΔIL6 mice (mean ± SEM; n = 6). *P < 0.05. The exercise (EX) time is presented. (B) The exercised CD- and HFD-fed (16 wk) mice were examined by GTTs (mean ± SEM; n = 6). (C) The exercised CD- and HFD-fed (16 wk.) mice were examined by ITTs (mean ± SEM; n = 6). (D) Total RNA was isolated from gWAT from CD- and HFD-fed MWT and MΔIL6 mice (16 wk). The relative expression of mRNA associated with macrophages (Adgre1 and Cd68), M1-like polarized macrophages (Ccl2, Cd11c, and Tnfα), and M2-like polarized macrophages (Arg1, Mgl1, Mgl2, Mrc1, and Mrc2) were measured by qRT-PCR assays (mean ± SEM; n = 5 ∼ 7). *P < 0.05; **P < 0.01; ***P < 0.001. (E) The relative expression of the receptor Ccr2 (and ligands Ccl2, Ccl7, and Ccl8) and the receptor Ccr5 (and ligands Ccl3, Ccl4, Ccl5, and Ccl8) were measured by qRT-PCR assays of mRNA (mean ± SEM; n = 5 ∼ 7). *P < 0.05; **P < 0.01. (F) The relative expression of IL6 pathway-associated genes (Socs3, Il6st, Il6rα, Adam10, and Adam17) by gWAT was measured by qRT-PCR assays of mRNA (mean ± SEM; n = 5 ∼ 8). *P < 0.05; **P < 0.01.
Fig. 7. Muscle IL6 suppresses the accumulation and M1-like polarization of ATMs. (A) The concentration of circulating IL6 in blood was measured from exercised CD- or HFD-fed (16 wk) MWT and MΔIL6 mice (mean ± SEM; n = 6). *P < 0.05. The exercise (EX) time is presented. (B) The exercised CD- and HFD-fed (16 wk) mice were examined by GTTs (mean ± SEM; n = 6). (C) The exercised CD- and HFD-fed (16 wk.) mice were examined by ITTs (mean ± SEM; n = 6). (D) Total RNA was isolated from gWAT from CD- and HFD-fed MWT and MΔIL6 mice (16 wk). The relative expression of mRNA associated with macrophages (Adgre1 and Cd68), M1-like polarized macrophages (Ccl2, Cd11c, and Tnfα), and M2-like polarized macrophages (Arg1, Mgl1, Mgl2, Mrc1, and Mrc2) were measured by qRT-PCR assays (mean ± SEM; n = 5 ∼ 7). *P < 0.05; **P < 0.01; ***P < 0.001. (E) The relative expression of the receptor Ccr2 (and ligands Ccl2, Ccl7, and Ccl8) and the receptor Ccr5 (and ligands Ccl3, Ccl4, Ccl5, and Ccl8) were measured by qRT-PCR assays of mRNA (mean ± SEM; n = 5 ∼ 7). *P < 0.05; **P < 0.01. (F) The relative expression of IL6 pathway-associated genes (Socs3, Il6st, Il6rα, Adam10, and Adam17) by gWAT was measured by qRT-PCR assays of mRNA (mean ± SEM; n = 5 ∼ 8). *P < 0.05; **P < 0.01.CC BY-NC-ND · PubMed Central

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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
Published
2020-01-24
Volume
117
Issue
6
Pages
2751-2760
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
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
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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