Deficiency of interleukin-18 in mice leads to hyperphagia, obesity and insulin resistance
Abstract
Here we report the presence of hyperphagia, obesity and insulin resistance in knockout mice deficient in IL-18 or IL-18 receptor, and in mice transgenic for expression of IL-18 binding protein. Obesity of Il18-/- mice resulted from accumulation of fat tissue based on increased food intake. Il18-/- mice also had hyperinsulinemia, consistent with insulin resistance and hyperglycemia. Insulin resistance was secondary to obesity induced by increased food intake and occurred at the liver level as well as at the muscle and fat-tissue level. The molecular mechanisms responsible for the hepatic insulin resistance in the Il18-/- mice involved an enhanced expression of genes associated with gluconeogenesis in the liver of Il18-/- mice, resulting from defective phosphorylation of STAT3. Recombinant IL-18 (rIL-18) administered intracerebrally inhibited food intake. In addition, rIL-18 reversed hyperglycemia in Il18-/- mice through activation of STAT3 phosphorylation. These findings indicate a new role of IL-18 in the homeostasis of energy intake and insulin sensitivity.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Local production of inflammatory molecules by adipose tissue within the heart may contribute to coronary pathologies because of its amount and proximity to coronary vessels.
“In this regard, the local production of the inflammatory molecules by adipose tissue within the heart may be important; the amount of this tissue and its proximity to the coronary vessels could contribute to the development of coronary pathologies (60,61) .”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [60]
Cites
Single-Step Method of RNA Isolation by Acid Guanidinium Thiocyanate–Phenol–Chloroform Extraction
Chomczynski, P., & Sacchi, N. (1987) · Analytical Biochemistry · doi:10.1006/abio.1987.9999 · Cited by 65,240 · see citing works
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction
Chomczyński, P., & Sacchi, N. (1987) · Analytical Biochemistry · doi:10.1016/0003-2697(87)90021-2 · Cited by 47,092 · see citing works
Yamauchi, T., Kamon, J., Waki, H., Terauchi, Y., Kubota, N., Hara, K., Mori, Y., Ide, T., Murakami, K., Tsuboyama-Kasaoka, N., et al. (2001) · Nature Medicine · doi:10.1038/90984 · Cited by 4,915 · see citing works
Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function.
Adachi, O., Kawai, T., Takeda, K., Matsumoto, M., Tsutsui, H., Sakagami, M., Nakanishi, K., & Akira, S. (1998) · Immunity · doi:10.1016/s1074-7613(00)80596-8 · Cited by 2,358 · see citing works
Self-citationEsposito, K., Nappo, F., Marfella, R., Giugliano, G., Giugliano, F., Ciotola, M., Quagliaro, L., Ceriello, A., & Giugliano, D. (2002) · Circulation · doi:10.1161/01.cir.0000034509.14906.ae · Cited by 1,961 · see citing works
Caspase-1 processes IFN-γ-inducing factor and regulates LPS-induced IFN- γ production
Ghayur, T., Banerjee, S., Hugunin, M., Butler, D., Herzog, L., Carter, A. B., Quintal, L. J., Sekut, L., Talanian, R. V., Paskind, M. P., et al. (1997) · Nature · doi:10.1038/386619a0 · Cited by 1,204 · see citing works
Defective NK Cell Activity and Th1 Response in IL-18–Deficient Mice
Takeda, K., Tsutsui, H., Yoshimoto, T., Adachi, O., Yoshida, N., Kishimoto, T., Okamura, H., Nakanishi, K., & Akira, S. (1998) · Immunity · doi:10.1016/s1074-7613(00)80543-9 · Cited by 911 · see citing works
Self-citationRole of Insulin Resistance in Human Disease (Syndrome X): An Expanded Definition
Reaven, G. M. (1993) · Annual Review of Medicine · doi:10.1146/annurev.me.44.020193.001005 · Cited by 911 · see citing works
Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat
Smith, S. J., Cases, S., Jensen, D. R., Chen, H. C., Sande, E., Tow, B., Sanan, D. A., Raber, J., Eckel, R. H., & Farese, R. V. (2000) · Nature Genetics · doi:10.1038/75651 · Cited by 895 · see citing works
Self-citationIL-18: A TH1 -inducing, proinflammatory cytokine and new member of the IL-1 family
Dinarello, C. A. (1999) · Journal of Allergy and Clinical Immunology · doi:10.1016/s0091-6749(99)70518-x · Cited by 817 · see citing works
Self-citationInterleukin-18 Binding Protein
Novick, D., Kim, S. H., Fantuzzi, G., Reznikov, L. L., Dinarello, C. A., & Rubinstein, M. (1999) · Immunity · doi:10.1016/s1074-7613(00)80013-8 · Cited by 781 · see citing works
Self-citationIshibashi, S., Goldstein, J. L., Brown, M. S., Herz, J., & Burns, D. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117179 · Cited by 731 · see citing works
The role of SOCS-3 in leptin signaling and leptin resistance
Bjørbæk, C., El-Haschimi, K., Frantz, J. D., & Flier, J. S. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.42.30059 · Cited by 639 · see citing works
Blaskovich, M. A., Sun, J., Cantor, A. B., Turkson, J., Jove, R., & Sebti, S. M. (2003) · PubMed · Cited by 567 · see citing works
Gao, Q., Wolfgang, M. J., Neschen, S., Morino, K., Horvath, T. L., Shulman, G. I., & Fu, X.-Y. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0303992101 · Cited by 385 · see citing works
Role of STAT-3 in regulation of hepatic gluconeogenic genes and carbohydrate metabolism in vivo
Inoue, H., Ogawa, W., Ozaki, M., Haga, S., Matsumoto, M., Furukawa, K., Hashimoto, N., Kido, Y., Mori, T., Sakaue, H., et al. (2004) · Nature Medicine · doi:10.1038/nm980 · Cited by 384 · see citing works
Self-citationUeki, K., Kondo, T., Tseng, Y., & Kahn, C. R. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402511101 · Cited by 382 · see citing works
Moriwaki, Y., Yamamoto, T., Shibutani, Y., Aoki, E., Tsutsumi, Z., Takahashi, S., Okamura, H., Koga, M., Fukuchi, M., & Hada, T. (2003) · Metabolism · doi:10.1053/meta.2003.50096 · Cited by 270 · see citing works
Netea, M. G., Fantuzzi, G., Kullberg, B. J., Stuyt, R. J. L., Pulido, E. J., McIntyre, R. C., Joosten, L. A. B., van der Meer, J. W. M., & Dinarello, C. A. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.5.2644 · Cited by 210 · see citing works
Self-citationEscobar-Morreale, H. F., Botella-Carretero, J. I., Villuendas, G., Sancho, J., & Millán, J. L. S. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031365 · Cited by 199 · see citing works
Miyake, K., Ogawa, W., Matsumoto, M., Nakamura, T., Sakaue, H., & Kasuga, M. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15880 · Cited by 155 · see citing works
Central Leptin Acutely Reverses Diet-Induced Hepatic Insulin Resistance
Pocai, A., Morgan, K., Buettner, C., Gutierrez-Juarez, R., Obici, S., & Rossetti, L. (2005) · Diabetes · doi:10.2337/diabetes.54.11.3182 · Cited by 153 · see citing works
Kalina, U., Kauschat, D., Koyama, N., Nuernberger, H., Ballas, K., Koschmieder, S., Bug, G., Hofmann, W., Hoelzer, D. F., & Ottmann, O. G. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.3.1307 · Cited by 136 · see citing works
An IFN-γ-Independent Proinflammatory Role of IL-18 in Murine Streptococcal Cell Wall Arthritis
Joosten, L. A. B., van de Loo, F. A. J., Lubberts, E., Helsen, M. M. A., Netea, M. G., van der Meer, J. W. M., Dinarello, C. A., & van den Berg, W. B. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.11.6553 · Cited by 119 · see citing works
Self-citationVoshol, P. J., Jong, M. C., Dahlmans, V. E. H., Kratky, D., Levak‐Frank, S., Zechner, R., Romijn, J. A., & Havekes, L. M. (2001) · Diabetes · doi:10.2337/diabetes.50.11.2585 · Cited by 116 · see citing works
Self-citationGorogawa, S.-I., Fujitani, Y., Kaneto, H., Hazama, Y., Watada, H., Miyamoto, Y., Takeda, K., Akira, S., Magnuson, M. A., Yamasaki, Y., et al. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.05.095 · Cited by 71 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Adipokines in inflammation and metabolic disease
Ouchi, N., Parker, J. L., Lugus, J. J., & Walsh, K. (2011) · Nature Reviews Immunology · doi:10.1038/nri2921 · Cited by 4,625 · see citing works
Immunological and inflammatory functions of the interleukin-1 family
Dinarello, C. A. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132612 · Cited by 3,466 · see citing works
Self-citationInflammasomes: mechanism of action, role in disease, and therapeutics
Guo, H., Callaway, J. B., & Ting, J. P.-Y. (2015) · Nature Medicine · doi:10.1038/nm.3893 · Cited by 3,340 · see citing works
Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity
Henao-Mejia, J., Elinav, E., Jin, C., Hao, L., Mehal, W. Z., Strowig, T., Thaiss, C. A., Kau, A. L., Eisenbarth, S. C., Jurczak, M. J., et al. (2012) · Nature · doi:10.1038/nature10809 · Cited by 2,435 · see citing works
Inflammasomes in health and disease
Strowig, T., Henao-Mejia, J., Elinav, E., & Flavell, R. (2012) · Nature · doi:10.1038/nature10759 · Cited by 2,230 · see citing works
The interleukin-1 family: back to the future
Garlanda, C., Dinarello, C. A., & Mantovani, A. (2013) · Immunity · doi:10.1016/j.immuni.2013.11.010 · Cited by 1,945 · see citing works
“IL-18 and IL-18R-deficient aged mice spontaneously develop a metabolic syndrome similar to that of humans with diabetes, insulin resistance, and atherosclerosis (Netea et al., 2006).”
Self-citationJung, U. J., & Choi, M. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms15046184 · Cited by 1,898 · see citing works
Overview of the <scp>IL</scp> ‐1 family in innate inflammation and acquired immunity
Dinarello, C. A. (2018) · Immunological Reviews · doi:10.1111/imr.12621 · Cited by 1,866 · see citing works
Self-citationObesity, Inflammation, and Insulin Resistance
Shoelson, S. E., Herrero, L., & Naaz, A. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.03.059 · Cited by 1,806 · see citing works
Dietary factors and low-grade inflammation in relation to overweight and obesity
Calder, P. C., Ahluwalia, N., Brouns, F., Buetler, T., Clement, K., Cunningham, K., Esposito, K., Jönsson, L. S., Kolb, H., Lansink, M., et al. (2011) · British Journal of Nutrition · doi:10.1017/s0007114511005460 · Cited by 1,098 · see citing works
Malnutrition and Infection: Complex Mechanisms and Global Impacts
Schaible, U. E., & Kaufmann, S. H. E. (2007) · PLoS Medicine · doi:10.1371/journal.pmed.0040115 · Cited by 958 · see citing works
Interleukin-18 and IL-18 Binding Protein
Dinarello, C. A., Novick, D., Kim, S., & Kaplanski, G. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00289 · Cited by 938 · see citing works
Self-citationHistorical insights into cytokines
Dinarello, C. A. (2007) · European Journal of Immunology · doi:10.1002/eji.200737772 · Cited by 926 · see citing works
Self-citationIL‐1, IL‐18, and IL‐33 families of cytokines
Arend, W. P., Palmer, G., & Gabay, C. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00624.x · Cited by 912 · see citing works
Inflammatory mechanisms in the regulation of insulin resistance
Tilg, H., & Moschen, A. R. (2008) · Molecular Medicine · doi:10.2119/2007-00119.tilg · Cited by 779 · see citing works
Inflammasome is a central player in the induction of obesity and insulin resistance
Stienstra, R., van Diepen, J. A., Tack, C. J., Zaki, M. H., van de Veerdonk, F. L., Perera, D., Neale, G. A., Hooiveld, G. J., Hijmans, A., Vroegrijk, I., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1100255108 · Cited by 727 · see citing works
Self-citationStienstra, R., Joosten, L. A. B., Koenen, T. B., van Tits, B. L. J. H., van Diepen, J. A., van den Berg, S. A. A., Rensen, P. C. N., Voshol, P. J., Fantuzzi, G., Hijmans, A., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.11.011 · Cited by 681 · see citing works
Self-citationCanonical Nlrp3 Inflammasome Links Systemic Low-Grade Inflammation to Functional Decline in Aging
Youm, Y.-H., Grant, R. W., McCabe, L. R., Albarado, D. C., Nguyen, K. Y., Ravussin, A., Pistell, P., Newman, S., Carter, R., Laque, A., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.09.010 · Cited by 674 · see citing works
Adipose Tissue-Derived Factors: Impact on Health and Disease
Trujillo, M. E., & Scherer, P. E. (2006) · Endocrine Reviews · doi:10.1210/er.2006-0033 · Cited by 611 · see citing works
Interleukin‐18: Biological properties and role in disease pathogenesis
Kaplanski, G. (2017) · Immunological Reviews · doi:10.1111/imr.12616 · Cited by 609 · see citing works
The Hormonal Control of Food Intake
Coll, A. P., Farooqi, I. S., & O’Rahilly, S. (2007) · Cell · doi:10.1016/j.cell.2007.04.001 · Cited by 605 · see citing works
Recent Advances on the Role of Cytokines in Atherosclerosis
Ait‐Oufella, H., Taleb, S., Mallat, Z., & Tedgui, A. (2011) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.110.207415 · Cited by 578 · see citing works
Epithelial IL-18 Equilibrium Controls Barrier Function in Colitis
Nowarski, R., Jackson, R. P., Gagliani, N., de Zoete, M. R., Palm, N. W., Bailis, W., Low, J. S., Harman, C. C. D., Graham, M. M., Elinav, E., et al. (2015) · Cell · doi:10.1016/j.cell.2015.10.072 · Cited by 564 · see citing works
Interleukin-18 in Health and Disease
Yasuda, K., Nakanishi, K., & Tsutsui, H. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20030649 · Cited by 564 · see citing works
Proteolytic Processing of Interleukin-1 Family Cytokines: Variations on a Common Theme
Afonina, I. S., Müller, C., Martin, S. J., & Beyaert, R. (2015) · Immunity · doi:10.1016/j.immuni.2015.06.003 · Cited by 483 · see citing works
Immunological complications of obesity
Kanneganti, T., & Dixit, V. D. (2012) · Nature Immunology · doi:10.1038/ni.2343 · Cited by 481 · see citing works
The role of adipokines in chronic inflammation
Mancuso, P. (2016) · ImmunoTargets and Therapy · doi:10.2147/itt.s73223 · Cited by 391 · see citing works
Targeting the NLRP3 inflammasome in chronic inflammatory diseases: current perspectives
Doyle, S., Ozaki, E., & Campbell, M. (2015) · Journal of Inflammation Research · doi:10.2147/jir.s51250 · Cited by 382 · see citing works
Inflammasome signaling and regulation of interleukin-1 family cytokines
Chan, A. H., & Schroder, K. (2019) · The Journal of Experimental Medicine · doi:10.1084/jem.20190314 · Cited by 374 · see citing works
Inflammasome, pyroptosis, and cytokines in myocardial ischemia-reperfusion injury
Toldo, S. A., Mauro, A. G., Cutter, Z., & Abbate, A. (2018) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00158.2018 · Cited by 373 · see citing works
The role of interleukins in insulin resistance and type 2 diabetes mellitus
Fève, B., & Bastard, J.-P. (2009) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2009.62 · Cited by 343 · see citing works
Targeting the NLRP3 inflammasome in cardiovascular diseases
Toldo, S. A., Mezzaroma, E., Buckley, L. F., Potere, N., Nisio, M. D., Biondi‐Zoccai, G., Tassell, B. W. V., & Abbate, A. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.108053 · Cited by 340 · see citing works
Role of IL-1β in type 2 diabetes
Dinarello, C. A., Donath, M. Y., & Mandrup-Poulsen, T. R. (2010) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0b013e32833bf6dc · Cited by 330 · see citing works
Self-citationToll-like receptors: linking inflammation to metabolism
Könner, A. C., & Brüning, J. C. (2010) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2010.08.007 · Cited by 327 · see citing works
Inflammasome-independent regulation of IL-1-family cytokines
Netea, M. G., van de Veerdonk, F. L., van der Meer, J. W. M., Dinarello, C. A., & Joosten, L. A. B. (2015) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032414-112306 · Cited by 326 · see citing works
Self-citationInterleukin-33 Induces Protective Effects in Adipose Tissue Inflammation During Obesity in Mice
Miller, A. M., Asquith, D. L., Hueber, A. J., Anderson, L. A., Holmes, W. M., McKenzie, A. N. J., Xu, D., Sattar, N. A., McInnes, I. B., & Liew, F. Y. (2010) · Circulation Research · doi:10.1161/circresaha.110.218867 · Cited by 323 · see citing works
Chronic adipose tissue inflammation: all immune cells on the stage
Cildir, G., Akıncılar, S. C., & Tergaonkar, V. (2013) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2013.05.001 · Cited by 317 · see citing works
Alboni, S., Cervia, D., Sugama, S., & Conti, B. (2010) · Journal of Neuroinflammation · doi:10.1186/1742-2094-7-9 · Cited by 301 · see citing works
NLRP3 at the interface of metabolism and inflammation
Haneklaus, M., & O'Neill, L. A. J. (2015) · Immunological Reviews · doi:10.1111/imr.12285 · Cited by 294 · see citing works
Focus on the Role of NLRP3 Inflammasome in Diseases
Fusco, R., Siracusa, R., Genovese, T., Cuzzocrea, S., & Paola, R. D. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124223 · Cited by 292 · see citing works
Cell death and inflammation during obesity: “Know my methods, WAT(son)”
Hildebrandt, X., Ibrahim, M. A., & Peltzer, N. (2022) · Cell Death and Differentiation · doi:10.1038/s41418-022-01062-4 · Cited by 283 · see citing works
Sensing damage by the NLRP3 inflammasome
Leemans, J. C., Cassel, S. L., & Sutterwala, F. S. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2011.01043.x · Cited by 281 · see citing works
Interleukin-18, more than a Th1 cytokine
Novick, D., Kim, S., Kaplanski, G., & Dinarello, C. A. (2013) · Seminars in Immunology · doi:10.1016/j.smim.2013.10.014 · Cited by 280 · see citing works
Self-citationThe Inflammasome Puts Obesity in the Danger Zone
Stienstra, R., Tack, C. J., Kanneganti, T., Joosten, L. A. B., & Netea, M. G. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2011.10.011 · Cited by 272 · see citing works
Self-citationBallak, D. B., Stienstra, R., Tack, C. J., Dinarello, C. A., & van Diepen, J. A. (2015) · Cytokine · doi:10.1016/j.cyto.2015.05.005 · Cited by 256 · see citing works
Self-citationInterleukin-18 and the Pathogenesis of Inflammatory Diseases
Dinarello, C. A. (2007) · Seminars in Nephrology · doi:10.1016/j.semnephrol.2006.09.013 · Cited by 249 · see citing works
Self-citationModulatory Mechanisms of the NLRP3 Inflammasomes in Diabetes
Ding, S., Xu, S., Ma, Y., Liu, G., Jang, H., & Fang, J. Q. (2019) · Biomolecules · doi:10.3390/biom9120850 · Cited by 241 · see citing works
Fatty Acids and NLRP3 Inflammasome–Mediated Inflammation in Metabolic Tissues
Ralston, J. C., Lyons, C. L., Kennedy, E. B., Kirwan, A. M., & Roche, H. M. (2017) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071816-064836 · Cited by 229 · see citing works
IL-37 protects against obesity-induced inflammation and insulin resistance
Ballak, D. B., van Diepen, J. A., Moschen, A. R., Jansen, H. J., Hijmans, A., Groenhof, G.-J., Leenders, F., Bufler, P., Boekschoten, M. V., Müller, M. M., et al. (2014) · Nature Communications · doi:10.1038/ncomms5711 · Cited by 221 · see citing works
Self-citationSugama, S., Fujita, M., Hashimoto, M., & Conti, B. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.02.043 · Cited by 216 · see citing works
Deficiency of a β-arrestin-2 signal complex contributes to insulin resistance
Luan, B., Zhao, J., Wu, H., Duan, B.-Y., Shu, G., Wang, X., Li, D., Jia, W., Kang, J., & Pei, G. (2009) · Nature · doi:10.1038/nature07617 · Cited by 216 · see citing works
Sharma, A., Tate, M., Mathew, G., Vince, J. E., Ritchie, R. H., & de Haan, J. B. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00114 · Cited by 216 · see citing works
IL-18 in autoimmunity: review.
Boraschi, D., & Dinarello, C. A. (2006) · PubMed · Cited by 208 · see citing works
Self-citationBiological and clinical roles of IL-18 in inflammatory diseases
Landy, E., Carol, H. A., Ring, A. M., & Canna, S. (2023) · Nature Reviews Rheumatology · doi:10.1038/s41584-023-01053-w · Cited by 206 · see citing works
NLRP3 inflammasome blockade reduces adipose tissue inflammation and extracellular matrix remodeling
Unamuno, X., Gómez‐Ambrosi, J., Ramírez, B., Rodrı́guez, A., Becerril, S., Valentí, V., Moncada, R., Silva, C., Salvador, J., Frühbeck, G., et al. (2019) · Cellular and Molecular Immunology · doi:10.1038/s41423-019-0296-z · Cited by 204 · see citing works
Innate sensors of pathogen and stress: Linking inflammation to obesity
Jin, C., & Flavell, R. A. (2013) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2013.06.022 · Cited by 195 · see citing works
Inflammation links excess fat to insulin resistance: the role of the interleukin‐1 family
Tack, C. J., Stienstra, R., Joosten, L. A. B., & Netea, M. G. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01145.x · Cited by 192 · see citing works
Self-citationImmune and inflammatory pathways in NASH
Ganz, M., & Szabó, G. (2013) · Hepatology International · doi:10.1007/s12072-013-9468-6 · Cited by 188 · see citing works
Innate Immune Receptors: Key Regulators of Metabolic Disease Progression
Jin, C., Henao‐Mejia, J., & Flavell, R. A. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.05.011 · Cited by 187 · see citing works
Inflammasomes: far beyond inflammation
Henao‐Mejia, J., Elinav, E., Strowig, T., & Flavell, R. A. (2012) · Nature Immunology · doi:10.1038/ni.2257 · Cited by 185 · see citing works
de Wit, N. J., Bosch-Vermeulen, H., de Groot, P. J., Hooiveld, G. J., Bromhaar, M. M. G., Jansen, J., Müller, M., & van der Meer, R. (2008) · BMC Medical Genomics · doi:10.1186/1755-8794-1-14 · Cited by 182 · see citing works
The NLRP1 and CARD8 inflammasomes
Taabazuing, C. Y., Griswold, A. R., & Bachovchin, D. A. (2020) · Immunological Reviews · doi:10.1111/imr.12884 · Cited by 178 · see citing works
How is inflammation initiated? Individual influences of IL-1, IL-18 and HMGB1
Keyel, P. A. (2014) · Cytokine · doi:10.1016/j.cyto.2014.03.007 · Cited by 175 · see citing works
Inflammasomes and Metabolic Disease
Henao‐Mejia, J., Elinav, E., Thaiss, C. A., & Flavell, R. A. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021113-170324 · Cited by 175 · see citing works
NLRP3 inflammasome activation in inflammaging
Latz, E., & Duewell, P. (2018) · Seminars in Immunology · doi:10.1016/j.smim.2018.09.001 · Cited by 174 · see citing works
Inflammation during obesity is not all bad: evidence from animal and human studies
Ye, J., & McGuinness, O. P. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00266.2012 · Cited by 173 · see citing works
IL-18 Production from the NLRP1 Inflammasome Prevents Obesity and Metabolic Syndrome
Murphy, A. J., Kraakman, M. J., Kammoun, H. L., Dragoljevic, D., Lee, M. K. S., Lawlor, K. E., Wentworth, J. M., Vasanthakumar, A., Gerlic, M., Whitehead, L. W., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.09.024 · Cited by 171 · see citing works
Interleukin-18 controls energy homeostasis by suppressing appetite and feed efficiency
Zorrilla, E. P., Sánchez-Alavez, M., Sugama, S., Brennan, M., Fernandez, R. E., Bartfai, T., & Conti, B. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0611523104 · Cited by 170 · see citing works
The IL-1 Pathway in Type 2 Diabetes and Cardiovascular Complications
Herder, C., Dalmas, É., Böni‐Schnetzler, M., & Donath, M. Y. (2015) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2015.08.001 · Cited by 169 · see citing works
Cytokine assays: An assessment of the preparation and treatment of blood and tissue samples
Keustermans, G., Hoeks, S. B. E. A., Meerding, J., Prakken, B. J., & de Jager, W. (2013) · Methods · doi:10.1016/j.ymeth.2013.04.005 · Cited by 166 · see citing works
Inflammasomes in neurological diseases: emerging pathogenic and therapeutic concepts
Mamik, M. K., & Power, C. (2017) · Brain : a journal of neurology · doi:10.1093/brain/awx133 · Cited by 151 · see citing works
Yazdi, A., & Ghoreschi, K. (2016) · Advances in Experimental Medicine and Biology · doi:10.1007/978-94-024-0921-5_2 · Cited by 192 · see citing works
The Therapeutic Potential of Modifying Inflammasomes and NOD-Like Receptors
Virgilio, F. D. (2013) · Pharmacological Reviews · doi:10.1124/pr.112.006171 · Cited by 158 · see citing works
The role of interleukin-18 in the metabolic syndrome
Trøseid, M., Seljeflot, I., & Arnesen, H. (2010) · Cardiovascular Diabetology · doi:10.1186/1475-2840-9-11 · Cited by 155 · see citing works
Pyroptosis in Liver Disease: New Insights into Disease Mechanisms
Wu, J., Lin, S., Wan, B., Velani, B., & Zhu, Y. (2019) · Aging and Disease · doi:10.14336/ad.2019.0116 · Cited by 155 · see citing works
IL-1 Family Cytokine Pathways Underlying NAFLD: Towards New Treatment Strategies
Mirea, A.-M., Tack, C. J., Chavakis, T., Joosten, L. A. B., & Toonen, E. J. M. (2018) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.03.005 · Cited by 144 · see citing works
Self-citationIL-1 family cytokines in inflammation and immunity
Garlanda, C., Ceglie, I. D., & Jaillon, S. (2025) · Cellular and Molecular Immunology · doi:10.1038/s41423-025-01358-8 · Cited by 143 · see citing works
A comprehensive pathway map of IL-18-mediated signalling
Balaya, R. D. A., Agarwal, N., Prasad, T. S. K., Kandasamy, R. K., Subbannayya, Y., & Pinto, S. M. (2019) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-019-00544-4 · Cited by 142 · see citing works
Microbiota, NASH, HCC and the potential role of probiotics
Brandi, G., Lorenzo, S. D., Candela, M., Pantaleo, M. A., Bellentani, S., Tovoli, F., Saccoccio, G., & Biasco, G. (2017) · Carcinogenesis · doi:10.1093/carcin/bgx007 · Cited by 141 · see citing works
The role of interferon-gamma in the increased tuberculosis risk in type 2 diabetes mellitus
Stalenhoef, J. E., Alisjahbana, B., Nelwan, E. J., van der Ven‐Jongekrijg, J., Ottenhoff, T. H. M., van der Meer, J. W. M., Nelwan, R. H. H., Netea, M. G., & Crevel, R. (2007) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/s10096-007-0395-0 · Cited by 136 · see citing works
Self-citationGregersen, S., Samocha‐Bonet, D., Heilbronn, L. K., & Campbell, L. V. (2012) · Journal of Nutrition and Metabolism · doi:10.1155/2012/238056 · Cited by 136 · see citing works
Papaetis, G. S., Papakyriakou, P., & Panagiotou, T. N. (2015) · Archives of Medical Science · doi:10.5114/aoms.2015.52350 · Cited by 135 · see citing works
Inflammasomes: sensors of metabolic stresses for vascular inflammation
Yang, X.-F. (2013) · Frontiers in Bioscience · doi:10.2741/4127 · Cited by 134 · 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
Ahechu, P., Zozaya, G., Martí, P., Hernández-Lizoáin, J. L., Baixauli, J., Unamuno, X., Frühbeck, G., & Catalán, V. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02918 · Cited by 129 · see citing works
The evolution of body fatness: trading off disease and predation risk
Speakman, J. R. (2018) · Journal of Experimental Biology · doi:10.1242/jeb.167254 · Cited by 118 · see citing works
Interleukin-15 contributes to the regulation of murine adipose tissue and human adipocytes
Barra, N. G., Reid, S., MacKenzie, R., Werstuck, G., Trigatti, B. L., Richards, C., Holloway, A. C., & Ashkar, A. A. (2010) · Obesity · doi:10.1038/oby.2009.445 · Cited by 116 · see citing works
Inflammasomes and Metabolic Disorders: Old Genes in Modern Diseases
Robbins, G. R., Wen, H., & Ting, J. P. ‐. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.03.029 · Cited by 114 · see citing works
Knight, S. F., Quigley, J. E., Yuan, J., Roy, S., Elmarakby, A. A., & Imig, J. D. (2007) · Hypertension · doi:10.1161/hypertensionaha.107.099499 · Cited by 113 · see citing works
Targeting the NLRP3 inflammasome–IL-1β pathway in type 2 diabetes and obesity
Meier, D. T., Souza, J. D. P., & Donath, M. Y. (2024) · Diabetologia · doi:10.1007/s00125-024-06306-1 · Cited by 113 · see citing works
Interleukin-18, the Metabolic Syndrome, and Subclinical Atherosclerosis
Zirlik, A., Abdullah, S. M., Gerdes, N., MacFarlane, L. A., Schönbeck, U., Khera, A., McGuire, D. K., Vega, G. L., Grundy, S. M., Libby, P., et al. (2007) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.107.149484 · Cited by 113 · see citing works
Lewis, E. C., Blaabjerg, L., Størling, J., Rønn, S. G., Mascagni, P., Dinarello, C. A., & Mandrup-Poulsen, T. R. (2011) · Molecular Medicine · doi:10.2119/molmed.2010.00152 · Cited by 112 · see citing works
Self-citationWang, J., Sun, C., Gerdes, N., Liu, C., Liao, M., Liu, J., Shi, M. A., He, A., Zhou, Y., Sukhova, G. K., et al. (2015) · Nature Medicine · doi:10.1038/nm.3890 · Cited by 111 · see citing works
Caputo, T., Gilardi, F., & Desvergne, B. (2017) · FEBS Letters · doi:10.1002/1873-3468.12742 · Cited by 111 · see citing works
Interleukin-18: a regulator of cancer and autoimmune diseases
Esmaeilbeig, M., & Ghaderi, A. A. (2017) · European Cytokine Network · doi:10.1684/ecn.2018.0401 · Cited by 111 · see citing works
Sugama, S., & Conti, B. (2007) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.11.003 · Cited by 111 · see citing works
The dual function of hepatic SOCS3 in insulin resistance in vivo
Torisu, T., Sato, N., Yoshiga, D., Kobayashi, T., Yoshioka, T., Mori, H., Iida, M., & Yoshimura, A. (2007) · Genes to Cells · doi:10.1111/j.1365-2443.2007.01044.x · Cited by 111 · see citing works
Role of Caspase-1 in the Pathogenesis of Inflammatory-Associated Chronic Noncommunicable Diseases
Molla, M. D., Akalu, Y., Geto, Z., Dagnew, B., Ayelign, B., & Shibabaw, T. (2020) · Journal of Inflammation Research · doi:10.2147/jir.s277457 · Cited by 110 · see citing works
Fat in flames: influence of cytokines and pattern recognition receptors on adipocyte lipolysis
Grant, R. W., & Stephens, J. M. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00053.2015 · Cited by 105 · see citing works
Lipids, inflammasomes, metabolism, and disease
Anand, P. (2020) · Immunological Reviews · doi:10.1111/imr.12891 · Cited by 104 · see citing works
- Authors
- Netea, M. G., Joosten, L. A. B., Lewis, E., Jensen, D. R., Voshol, P. J., Kullberg, B. J., Tack, C. J., van Krieken, H., Kim, S.-H., Stalenhoef, A. F., van de Loo, F. A., Verschueren, I., Pulawa, L., Akira, S., Eckel, R. H., Dinarello, C. A., van den Berg, W., & van der Meer, J. W. M.
- Affiliations
- Radboud University Nijmegen (NL)
- University of Colorado Denver (US)
- University of Colorado Health (US)
- Leiden University Medical Center (NL)
- Research Institute for Microbial Diseases, The University of Osaka (JP)
- Corresponding author
- Netea, Mihai G
- ORCID
- Venue
- Nature Medicine
- Published
- 2006-05-28
- Volume
- 12
- Issue
- 6
- Pages
- 650-656
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2117361576
- Semantic Scholar
- 4e31e4c0a0d155e2768fb7d83aba11acd247f4bc
- Cited by
- 424
- References
- 25
- Citations by year
- 2026: 11 · 2025: 21 · 2024: 17 · 2023: 12 · 2022: 15 · 2021: 18 · 2020: 18 · 2019: 23 · 2018: 30 · 2017: 16 · 2016: 24 · 2015: 27 · 2014: 20 · 2013: 38 · 2012: 27
- FWCI
- 9.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- IL-18, IL-18 receptor, IL-18 binding protein, hyperphagia, obesity, insulin resistance, hyperinsulinemia, hyperglycemia, hepatic insulin resistance, STAT3 phosphorylation, gluconeogenesis, food intake regulation, energy homeostasis, knockout mice
- MeSH terms
- Animals, Body Weight, Eating, Energy Metabolism, Gluconeogenesis, Glucose, Glycoproteins, Homeostasis, Hyperphagia, Insulin Resistance, Liver, Mice, Inbred C57BL, Mice, Transgenic, Obesity, Recombinant Proteins, Receptors, Interleukin, Mice, Knockout, Interleukin-18, Intercellular Signaling Peptides and Proteins, STAT3 Transcription Factor, Mice, Receptors, Interleukin-18, Interleukin-18 Receptor alpha Subunit
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review