Interleukin-6 signaling in liver-parenchymal cells suppresses hepatic inflammation and improves systemic insulin action
Open accessAbstract
The contribution of interleukin (IL)-6 signaling in obesity-induced inflammation remains controversial. To specifically define the role of hepatic IL-6 signaling in insulin action and resistance, we have generated mice with hepatocyte-specific IL-6 receptor (IL-6R) alpha deficiency (IL-6Ralpha(L-KO) mice). These animals showed no alterations in body weight and fat content but exhibited a reduction in insulin sensitivity and glucose tolerance. Impaired glucose metabolism originated from attenuated insulin-stimulated glucose transport in skeletal muscle and fat. Surprisingly, hepatic IL-6Ralpha-disruption caused an exaggerated inflammatory response during euglycemic hyperinsulinemic clamp analysis, as revealed by increased expression of IL-6, TNF-alpha, and IL-10, as well as enhanced activation of inflammatory signaling such as phosphorylation of IkappaBalpha. Neutralization of TNF-alpha or ablation of Kupffer cells restored glucose tolerance in IL-6Ralpha(L-KO) mice. Thus, our results reveal an unexpected role for hepatic IL-6 signaling to limit hepatic inflammation and to protect from local and systemic insulin resistance.
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Il6raf/fΔAlb animals lacking hepatic IL6 signaling were significantly more sensitive to endotoxemia regardless of stress-priming.
“Here, regardless of stress-priming, animals lacking hepatic IL6 signaling were significantly more sensitive to endotoxemia, suggesting that the hepatic acute phase response was a required adaptation to endotoxemia (Figure S5B), consistent with previous reports (Castell et al., 1989; Wunderlich et al., 2010).”
From Origin and function of stress-induced IL-6 in murine models (2020) · cites this paper as Wunderlich et al., 2010
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“In contrast, mice with a liverspecific deletion of the IL-6 receptor a gene exhibited reduced insulin sensitivity and glucose tolerance (98), suggesting that IL-6 at low concentration has permissive effects on insulin sensitivity and glucose metabolism, but at high concentration detrimental effects.”
BackgroundFrom cytokine to myokine: The emerging role of interleukin-6 in metabolic regulation
Pal, M., Febbraio, M. A., & Whitham, M. (2014) · Immunology & Cell Biology · doi:10.1038/icb.2014.16 · Cited by 258 · see citing works
Kraakman, M. J., Kammoun, H. L., Allen, T. L., Deswaerte, V., Henstridge, D. C., Estevez, E., Matthews, V. B., Neill, B., White, D. A., Murphy, A. J., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.02.006 · Cited by 257 · see citing works
“, 2010) or via liver-specific deletion of the IL-6 receptor (Wunderlich et al., 2010) results in”
BackgroundNeuronal control of peripheral insulin sensitivity and glucose metabolism
Ruud, J., Steculorum, S. M., & Brüning, J. C. (2017) · Nature Communications · doi:10.1038/ncomms15259 · Cited by 245 · see citing works
Self-citationIL-6 Improves Energy and Glucose Homeostasis in Obesity via Enhanced Central IL-6 trans-Signaling
Timper, K., Denson, J. L., Steculorum, S. M., Heilinger, C., Engström, L., Wunderlich, C. M., Rose‐John, S., Wunderlich, F. T., & Brüning, J. C. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.03.043 · Cited by 233 · see citing works
IL-6 Regulates M2 Polarization and Local Proliferation of Adipose Tissue Macrophages in Obesity
Braune, J., Weyer, U., Hobusch, C., Mauer, J., Brüning, J. C., Bechmann, I., & Gericke, M. T. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1600476 · Cited by 237 · see citing works
Clonal haematopoiesis and risk of chronic liver disease
Wong, W. J., Emdin, C. A., Bick, A. G., Zekavat, S. M., Niroula, A., Pirruccello, J. P., Dichtel, L. E., Griffin, G. K., Uddin, M. M., Gibson, C. J., et al. (2023) · Nature · doi:10.1038/s41586-023-05857-4 · Cited by 221 · see citing works
Macrophage function in obesity-induced inflammation and insulin resistance
Lauterbach, M., & Wunderlich, F. T. (2017) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-017-1955-5 · Cited by 209 · see citing works
“Furthermore, inflammatory TNFα released by hepatic macrophages limits systemic insulin action, and IL-6 signaling in hepatocytes instructs downregulation of the inflammatory response in hepatic macrophages [120].”
BackgroundGehrke, N., & Schattenberg, J. M. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.02.020 · Cited by 211 · see citing works
Vogt, M. C., & Brüning, J. C. (2012) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2012.11.004 · Cited by 188 · see citing works
Wunderlich, C. M., Ackermann, P., Ostermann, A. L., Adams‐Quack, P., Vogt, M. C., Tran, M.-L., Nikolajev, A., Waisman, A., Garbers, C., Theurich, S., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03773-0 · Cited by 178 · see citing works
Xie, Z., Hao, H., Tong, C., Cheng, Y., Liu, J., Pang, Y., Si, Y., Guo, Y., Zang, L., Mu, Y., et al. (2015) · Stem Cells · doi:10.1002/stem.2238 · Cited by 178 · see citing works
The Metabolically Benign and Malignant Fatty Liver
Stefan, N., & Häring, H. (2011) · Diabetes · doi:10.2337/db11-0231 · Cited by 172 · see citing works
“In this aspect, it was shown that mice with hepatic deficiency of interleukin-6 receptor a (IL-6Ra) unexpectedly developed insulin resistance in liver, skeletal muscle, and white adipose tissue (33).”
BackgroundMiller, A. M., Wang, H., Bertola, A., Park, O., Horiguchi, N., Ki, S. H., Yin, S., Lafdil, F., & Gao, B. (2011) · Hepatology · doi:10.1002/hep.24517 · Cited by 162 · see citing works
“By using hepatocytespecific IL-6 receptor knockout mice, Wunderlich et al.(42) recently also reported that IL-6 acts as an antiinflammatory cytokine by targeting hepatocytes.”
MethodNew insights into IL-6 family cytokines in metabolism, hepatology and gastroenterology
Giraldez, M. D., Carneros, D., Garbers, C., Rose-John, S., & Bustos, M. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00473-x · Cited by 156 · see citing works
Nonalcoholic fatty liver disease: A main driver of insulin resistance or a dangerous liaison?
Gruben, N., Shiri‐Sverdlov, R., Koonen, D. P. Y., & Hofker, M. H. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.08.004 · Cited by 153 · see citing works
The exercise IL-6 enigma in cancer
Orange, S. T., Leslie, J., Ross, M., Mann, D. A., & Wackerhage, H. (2023) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2023.08.001 · Cited by 149 · see citing works
Toll-like receptors, inflammation, metabolism and obesity
Fresno, M., Álvarez, R., & Cuesta, N. (2011) · Archives of Physiology and Biochemistry · doi:10.3109/13813455.2011.562514 · Cited by 145 · see citing works
“Moreover, IL-6 in the liver suppresses hepatic inflammation and improves systemic insulin sensitivity (Wunderlich et al., 2010).”
BackgroundSchmitz, J., Evers, N., Awazawa, M., Nicholls, H. T., Brönneke, H. S., Dietrich, A., Mauer, J., Blüher, M., & Brüning, J. C. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2015.12.001 · Cited by 148 · see citing works
Self-citationT cell-intrinsic role of IL-6 signaling in primary and memory responses
Nish, S. A., Schenten, D., Wunderlich, F. T., Pope, S. D., Gao, Y., Hoshi, N., Yu, S., Yan, X., Lee, H. K., Pasman, L., et al. (2014) · eLife · doi:10.7554/elife.01949 · Cited by 145 · see citing works
“The generation of the conditional Il6ra allele has been published previously (Wunderlich et al., 2010).”
BackgroundMuscle-derived interleukin 6 increases exercise capacity by signaling in osteoblasts
Chowdhury, S., Schulz, L., Palmisano, B., Singh, P. P., Berger, J. M., Yadav, V. K., Mera, P., Ellingsgaard, H., Hidalgo, J., Brüning, J. C., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci133572 · Cited by 148 · see citing works
Physiological effects of modulating the interleukin-6 axis
Schett, G. A. (2018) · Rheumatology · doi:10.1093/rheumatology/kex513 · Cited by 142 · see citing works
Tamura, Y., Watanabe, K., Kantani, T., Hayashi, J., Ishida, N., & Kaneki, M. (2011) · Endocrine Journal · doi:10.1507/endocrj.k10e-400 · Cited by 137 · see citing works
“In previous studies [2-5], plasma IL-15 was measured starting at 1 h post-exercise.”
BackgroundMethodResultInfluentialInnate Immune Cells in the Adipose Tissue in Health and Metabolic Disease
Michailidou, Z., Gomez-Salazar, M. A., & Alexaki, V. I. (2021) · Journal of Innate Immunity · doi:10.1159/000515117 · Cited by 137 · see citing works
Role of interleukins in obesity: implications for metabolic disease
Febbraio, M. A. (2014) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2014.02.004 · Cited by 130 · see citing works
Protectin DX alleviates insulin resistance by activating a myokine-liver glucoregulatory axis
White, P. J., St‐Pierre, P., Charbonneau, A., Mitchell, P. L., St-Amand, E., Marcotte, B., & Marette, A. (2014) · Nature Medicine · doi:10.1038/nm.3549 · Cited by 130 · see citing works
“Our data thus join a growing body of work 5,12,16,17 that argues for a positive role of IL-6 in the regulation of glucose metabolism.”
Özcan, N., Karaman, C., Atar, N., Karaman, O., & Yola, M. L. (2020) · ECS Journal of Solid State Science and Technology · doi:10.1149/2162-8777/abd149 · Cited by 130 · see citing works
Non-cell-autonomous activation of IL-6/STAT3 signaling mediates FGF19-driven hepatocarcinogenesis
Zhou, M., Yang, H., Learned, R. M., Tian, H., & Ling, L. (2017) · Nature Communications · doi:10.1038/ncomms15433 · Cited by 123 · see citing works
Revisiting the role of Akkermansia muciniphila as a therapeutic bacterium
Si, J., Kang, H., You, H. J., & Ko, G. (2022) · Gut Microbes · doi:10.1080/19490976.2022.2078619 · Cited by 126 · see citing works
“processes such as hepatic inflammation and glucose homeostasis via BAT.(50,51) In human subjects, it was also recently shown to delay gastric emptying and, consequently, postprandial insulin secretion.”
BackgroundKnier, B., Hiltensperger, M., Sie, C., Aly, L., Lepennetier, G., Engleitner, T., Garg, G., Muschaweckh, A., Mitsdoerffer, M., Koedel, U., et al. (2018) · Nature Immunology · doi:10.1038/s41590-018-0237-5 · Cited by 121 · see citing works
Adiponectin: A Promising Target for the Treatment of Diabetes and Its Complications
Begum, M., Choubey, M., Tirumalasetty, M. B., Arbee, S., Mohib, M. M., Wahiduzzaman, M., Mamun, M. A., Uddin, M. B., & Mohiuddin, M. S. (2023) · Life · doi:10.3390/life13112213 · Cited by 128 · see citing works
“Furthermore, the differential gene expression was computed between these groups and represented as a dot plot as depicted in Figure 5C.”
MethodTheurich, S., Tsaousidou, E., Hanßen, R., Lempradl, A. M., Mauer, J., Timper, K., Schilbach, K., Folz‐Donahue, K., Heilinger, C., Sexl, V., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.05.018 · Cited by 120 · see citing works
Rui, K., Hong, Y., Zhu, Q., Shi, X., Xiao, F., Fu, H., Yin, Q., Xing, Y., Wu, X., Kong, X., et al. (2021) · Cellular and Molecular Immunology · doi:10.1038/s41423-020-00587-3 · Cited by 118 · see citing works
Mechanisms of chronic JAK-STAT3-SOCS3 signaling in obesity
Wunderlich, C. M., Hövelmeyer, N., & Wunderlich, F. T. (2013) · JAK-STAT · doi:10.4161/jkst.23878 · Cited by 176 · see citing works
The roles of c‐Jun NH2‐terminal kinases (JNKs) in obesity and insulin resistance
Pál, M., Febbraio, M. A., & Lancaster, G. I. (2015) · The Journal of Physiology · doi:10.1113/jp271457 · Cited by 114 · see citing works
“However, the detrimental effects of the above described hepatic IL-6 signalling on insulin resistance have been challenged using mice that lack the IL-6 receptor α specifically in the liver (Wunderlich et al. 2010).”
BackgroundFrisdal, É., Lesnik, P., Olivier, M., Robillard, P., Chapman, M. J., Huby, T., Guérin, M., & Goff, W. L. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.264325 · Cited by 114 · see citing works
Lipolytic and thermogenic depletion of adipose tissue in cancer cachexia
Tsoli, M., Swarbrick, M. M., & Robertson, G. R. (2015) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2015.10.039 · Cited by 109 · see citing works
Ling, J., Chaba, T., Zhu, L.-F., Jacobs, R. L., & Vance, D. E. (2011) · Hepatology · doi:10.1002/hep.24782 · Cited by 104 · see citing works
“Of note, IL-6 inhibits insulin-stimulated glycogen synthesis in rat hepatocytes.(38) Therefore, the inflammatory response induced by low hepatic PC/PE in HF-fed Pemt / mice may also contribute to mortality after PH by impairing glycogen storage.”
BackgroundCimini, F. A., Barchetta, I., Carotti, S., Bertoccini, L., Baroni, M. G., Vespasiani-Gentilucci, U., Cavallo, M.-G., & Morini, S. (2017) · World Journal of Gastroenterology · doi:10.3748/wjg.v23.i19.3407 · Cited by 101 · see citing works
The role of interleukin-6 in glucose homeostasis and lipid metabolism
Lehrskov, L. L., & Christensen, R. H. (2019) · Seminars in Immunopathology · doi:10.1007/s00281-019-00747-2 · Cited by 114 · see citing works
Mesenteric Fat Lipolysis Mediates Obesity-Associated Hepatic Steatosis and Insulin Resistance
Wueest, S., Item, F., Lucchini, F. C., Challa, T. D., Müller, W., Blüher, M., & Konrad, D. (2015) · Diabetes · doi:10.2337/db15-0941 · Cited by 98 · see citing works
“Although we are aware that knockout of gp130 in adipocytes affects the signaling pathway of all members of the IL-6 cytokines, the mouse model still seems adequate to investigate our hypothesis because the mIL-6R is not expressed in adipocytes (7), precluding cell-specific depletion of IL-6 signaling in adipocytes sim…”
BackgroundResultDiet-induced gut dysbiosis and inflammation: Key drivers of obesity-driven NASH
Kang, G. G., Trevaskis, N. L., Murphy, A. J., & Febbraio, M. A. (2023) · iScience · doi:10.1016/j.isci.2022.105905 · Cited by 94 · see citing works
Yekollu, S. K., Thomas, R., & O’Sullivan, B. (2011) · Diabetes · doi:10.2337/db11-0275 · Cited by 92 · see citing works
Liver innate immune cells and insulin resistance: the multiple facets of Kupffer cells
Jager, J., Aparicio‐Vergara, M., & Aouadi, M. (2016) · Journal of Internal Medicine · doi:10.1111/joim.12483 · Cited by 90 · see citing works
IL-6 receptor blockade ameliorates diabetic nephropathy via inhibiting inflammasome in mice
Wu, R., Liu, X., Yin, J., Wu, H., Cai, X., Wang, N., Qian, Y., & Wang, F. (2018) · Metabolism · doi:10.1016/j.metabol.2018.01.002 · Cited by 90 · see citing works
Xu, E., Pereira, M. M. A., Karakasilioti, I., Theurich, S., Al-Maarri, M., Rappl, G., Waisman, A., Wunderlich, F. T., & Brüning, J. C. (2017) · Nature Communications · doi:10.1038/ncomms14803 · Cited by 89 · see citing works
“To generate mice with T cell-specific IL-6R a deficiency (IL-6R a T-KO ), we crossed mice hemizygous for a transgene in which transcription of the Cre recombinase is controlled by the Cd4 promoter (CD4-Cre) 26 with mice homozygous for LoxP -flanked Il6ra alleles (IL-6R a f/f ) 27 .”
Silva, A. S., & Peixoto, C. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2838-4 · Cited by 85 · see citing works
“The dysregulated release of cytokines following liver damage may result in the excessive death of hepatocytes, which is a key event in several acute and chronic liver diseases [17].”
BackgroundInfluentialSignaling pathways and intervention for therapy of type 2 diabetes mellitus
Cao, R. Y., Tian, H., Zhang, Y., Liu, G., Xu, H., Rao, G., Tian, Y., & Fu, X. (2023) · MedComm · doi:10.1002/mco2.283 · Cited by 92 · see citing works
Interleukin-6 gene transfer reverses body weight gain and fatty liver in obese mice
Ma, Y., Gao, M., Sun, H. Y., & Liu, D. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.01.017 · Cited by 90 · see citing works
Atar, N., & Yola, M. L. (2021) · Analytica Chimica Acta · doi:10.1016/j.aca.2021.338202 · Cited by 87 · see citing works
A subcutaneous adipose tissue–liver signalling axis controls hepatic gluconeogenesis
Reilly, S. M., Ahmadian, M., Zamarron, B. F., Chang, L. C., Uhm, M., Poirier, B., Peng, X., Krause, D., Korytnaya, E., Neidert, A., et al. (2015) · Nature Communications · doi:10.1038/ncomms7047 · Cited by 84 · see citing works
“IL-6 signalling has previously been shown to have anti-inflammatory effects in liver as well as inflammatory cells 24,25 .”
Buechler, C., Haberl, E. M., Rein‐Fischboeck, L., & Aslanidis, C. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18071392 · Cited by 84 · see citing works
“On the other hand, IL-6 signaling specifically in hepatocytes protects the animals from hepatic inflammation and insulin resistance [169] (Figure 2).”
BackgroundLipid Sensing and Insulin Resistance in the Brain
Yue, J. T. Y., & Lam, T. K. T. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.01.013 · Cited by 82 · see citing works
Efeito do exercício no sistema imune: resposta, adaptação e sinalização celular
Terra, R., Da-Silva, S. A. G., Salerno, V. P., & Dutra, P. M. L. (2012) · Revista Brasileira de Medicina do Esporte · doi:10.1590/s1517-86922012000300015 · Cited by 80 · see citing works
Adipokines in obesity and metabolic-related-diseases
Pestel, J., Blangero, F., Watson, J., Pirola, L., & Eljaafari, A. (2023) · Biochimie · doi:10.1016/j.biochi.2023.04.008 · Cited by 80 · see citing works
Becker, M., Joseph, S. S., García‐Carrizo, F., Tom, R. Z., Opaleva, D., Serr, I., Tschöp, M. H., Schulz, T. J., Hofmann, S. M., & Daniel, C. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.08.010 · Cited by 73 · see citing works
Fucoidan from sea cucumber may improve hepatic inflammatory response and insulin resistance in mice
Wang, J., Hu, S., Jiang, W., Song, W., Cai, L., & Wang, J. (2015) · International Immunopharmacology · doi:10.1016/j.intimp.2015.12.009 · Cited by 72 · see citing works
Anti-Inflammatory Effect of Resveratrol in Old Mice Liver
Tung, B. T., Rodríguez-Bies, E., Talero, E., Gamero-Estévez, E., Motilva, V., Navas, P., & López-Lluch, G. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2015.02.004 · Cited by 71 · see citing works
“Among these factors, IL-6 is a cytokine with pleiotropic effects and its increase is associated with chronic inflammations, autoimmune diseases, and hematopoietic disorders (Wunderlich et al., 2010).”
BackgroundDeficiency in Interferon-γ Results in Reduced Body Weight and Better Glucose Tolerance in Mice
Wong, N., Fam, B. C., Cempako, G. R., Steinberg, G. R., Walder, K. R., Kay, T. W. H., Proietto, J., & Andrikopoulos, S. (2011) · Endocrinology · doi:10.1210/en.2011-0288 · Cited by 70 · see citing works
Kim, Y. D., Kim, Y. H., Cho, Y. M., Kim, D. K., Ahn, S.-W., Lee, J., Chanda, D., Shong, M., Lee, C., & Choi, H.-S. (2012) · Diabetologia · doi:10.1007/s00125-012-2494-4 · Cited by 70 · see citing works
The human longevity gene homolog INDY and interleukin‐6 interact in hepatic lipid metabolism
von Loeffelholz, C., Lieske, S., Neuschäfer‐Rube, F., Willmes, D. M., Raschzok, N., Sauer, I. M., König, J., Fromm, M. F., Horn, P., Chatzigeorgiou, A., et al. (2017) · Hepatology · doi:10.1002/hep.29089 · Cited by 68 · see citing works
“In these animals, a compensatory increase in many other cytokines has been reported.((21)) In contrast, low-dose application of murine IL-6 in mice leads to hepatic steatosis.”
BackgroundMethodInfluentialThe biology behind interleukin-6 targeted interventions
Liu, X., Jones, G. W., Choy, E., & Jones, S. A. (2016) · Current Opinion in Rheumatology · doi:10.1097/bor.0000000000000255 · Cited by 70 · see citing works
Exerkines and cardiometabolic benefits of exercise: from bench to clinic
Jin, L., Díaz-Cañestro, C., Wang, Y., Tse, M. A., & Xu, A. (2024) · EMBO Molecular Medicine · doi:10.1038/s44321-024-00027-z · Cited by 68 · see citing works
“For example, mice with hepatocyte-speci fi c IL-6RA de fi ciency displayed systemic insulin resistance and notable hepatic in fl am-mation even under a normal diet (Wunderlich et al, 2010).”
Background
- Authors
- Wunderlich, F. T., Ströhle, P., Könner, A. C., Gruber, S., Tovar, S., Brönneke, H. S., Juntti-Berggren, L., Li, L.-S., van Rooijen, N., Libert, C., Berggren, P.-O., & Brüning, J. C.
- Affiliations
- University of Cologne (DE)
- Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (DE)
- Karolinska Institutet (SE)
- Vlaams Instituut voor Biotechnologie (BE)
- Corresponding author
- Brüning, Jens C.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2010-09
- Volume
- 12
- Issue
- 3
- Pages
- 237-249
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2090699565
- Cited by
- 229
- References
- 48
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 11 · 2023: 12 · 2022: 12 · 2021: 13 · 2020: 15 · 2019: 17 · 2018: 22 · 2017: 21 · 2016: 12 · 2015: 15 · 2014: 14 · 2013: 12 · 2012: 18
- FWCI
- 10.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1086 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (1492-7-1, SFB 635, SFB 832)
- Novartis Foundation
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- IL-6 signaling, IL-6 receptor alpha, hepatocytes, liver inflammation, insulin resistance, insulin sensitivity, glucose tolerance, TNF-α, Kupffer cells, obesity-associated inflammation, insulin-stimulated glucose transport, NF-κB signaling, skeletal muscle, adipose tissue
- MeSH terms
- Animals, Energy Metabolism, Glucose, Glycogen, Homeostasis, Humans, Inflammation, Insulin, Insulin Resistance, Kupffer Cells, Liver, Tumor Necrosis Factor-alpha, Signal Transduction, Interleukin-6, Interleukin-10, Mice, Knockout, Receptors, Interleukin-6, Adiposity, Mice
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