Cited by 4,143Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismImmune cells in cancer

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Inflammation, stress, and diabetes

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Wellen, Kathryn E., Hotamisligil, Gökhan S.·2005·Journal of Clinical Investigation

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Abstract

Over the last decade, an abundance of evidence has emerged demonstrating a close link between metabolism and immunity.It is now clear that obesity is associated with a state of chronic low-level inflammation.In this article, we discuss the molecular and cellular underpinnings of obesity-induced inflammation and the signaling pathways at the intersection of metabolism and inflammation that contribute to diabetes.We also consider mechanisms through which the inflammatory response may be initiated and discuss the reasons for the inflammatory response in obesity.We put forth for consideration some hypotheses regarding important unanswered questions in the field and suggest a model for the integration of inflammatory and metabolic pathways in metabolic disease. Inflammation, stress, and diabetesSurvival of multicellular organisms depends on the ability to fight infection and heal damage and the ability to store energy for times of low nutrient availability or high energy need.Metabolic and immune systems are therefore among the most basic requirements across the animal kingdom, and many nutrient and pathogen-sensing systems have been highly conserved from organisms such as Caenorhabditis elegans and Drosophila to mammals.Perhaps not surprisingly, metabolic and immune pathways have also evolved to be closely linked and interdependent.Many hormones, cytokines, signaling proteins, transcription factors, and bioactive lipids can function in both metabolic and immune roles.In addition to using some of the same cellular machinery, metabolic and immune systems also regulate each other.The normal inflammatory response relies upon metabolic support, and energy redistribution, particularly the mobilization of stored lipid, plays an important role in fighting infection during the acute-phase response (1).The basic inflammatory response thus favors a catabolic state and suppresses anabolic pathways, such as the highly conserved and powerful insulin signaling pathway.The integration of metabolism and immunity, which under normal conditions is beneficial for the maintenance of good health, can become deleterious under conditions of metabolic challenge, as exemplified by the immunosuppression characteristic of malnourished or starving individuals (1-3).Famine has been a prominent hazard to human health throughout history, and for thousands of years the link between infection and poor nutrition has been well recognized.Today this threat is as widespread as ever, and there are approximately 1 billion undernourished individuals worldwide (3).In the past century, however, the pendulum has also swung in the opposite direction, and now as many if not more people are overweight or obese (4).With the advent of this chronic metabolic overload, a new set of problems and complications at the intersection of metabolism and immunity has emerged, including the obesity-linked inflammatory diseases diabetes, fatty liver disease, airway inflammation, and atherosclerosis (5).There is now a wealth of evidence indicating close ties between metabolic and immune systems.Among the many reasons to

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1 retracted

Visfatin: A Protein Secreted by Visceral Fat That Mimics the Effects of Insulin
Fukuhara, A., Matsuda, M., Nishizawa, M., Segawa, K., Tanaka, M., Kishimoto, K., Matsuki, Y., Murakami, M., Ichisaka, T., Murakami, H., et al. (2005) · Science · doi:10.1126/science.1097243 · Cited by 1,906
Retracted
Obesity is associated with macrophage accumulation in adipose tissue
Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., & Ferrante, A. W. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319246 · Cited by 10,041
Biochemistry and molecular cell biology of diabetic complications
Brownlee, M. (2001) · Nature · doi:10.1038/414813a · Cited by 9,107
Adipose Expression of Tumor Necrosis Factor-α: Direct Role in Obesity-Linked Insulin Resistance
Hotamisligil, G. S., Shargill, N. S., & Spiegelman, B. M. (1993) · Science · doi:10.1126/science.7678183 · Cited by 7,518
Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance
Xu, H., Barnes, G. T., Yang, Q., Tan, G., Yang, D., Chou, C. J., Sole, J., Nichols, A., Ross, J. S., Tartaglia, L. A., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319451 · Cited by 6,760
Increased oxidative stress in obesity and its impact on metabolic syndrome
Furukawa, S., Fujita, T., Shimabukuro, M., Iwaki, M., Yamada, Y., Nakajima, Y., Nakayama, O., Makishima, M., Matsuda, M., & Shimomura, I. (2004) · Journal of Clinical Investigation · doi:10.1172/jci21625 · Cited by 5,508
Toll-like receptors and innate immunity
Medzhitov, R. (2001) · Nature Reviews Immunology · doi:10.1038/35100529 · Cited by 4,308
Signal transduction by the JNK group of MAP kinases
Davis, R. J. (2000) · Cell · doi:10.1016/s0092-8674(00)00116-1 · Cited by 4,237
Endoplasmic Reticulum Stress Links Obesity, Insulin Action, and Type 2 Diabetes
Özcan, U., Cao, Q., Yilmaz, E., Lee, A.-H., Iwakoshi, N. N., Özdelen, E., Tuncman, G., Görgün, C., Glimcher, L. H., & Hotamisligil, G. S. (2004) · Science · doi:10.1126/science.1103160 · Cited by 3,844
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837

Show all 118 references

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Hotamisligil, G. S. (2006) · Nature · doi:10.1038/nature05485 · Cited by 9,199
A metagenome-wide association study of gut microbiota in type 2 diabetes
Qin, J., Li, Y., Cai, Z., Li, S., Zhu, J., Zhang, F., Liang, S., Zhang, W., Guan, Y., Shen, D., et al. (2012) · Nature · doi:10.1038/nature11450 · Cited by 6,762
Metabolic Endotoxemia Initiates Obesity and Insulin Resistance
Cani, P. D., Amar, J., Iglesias, M. A., Poggi, M., Knauf, C., Bastelica, D., Neyrinck, A. M., Fava, F., Tuohy, K. M., Chabo, C., et al. (2007) · Diabetes · doi:10.2337/db06-1491 · Cited by 6,638
Adipose Tissue as an Endocrine Organ
Kershaw, E. E., & Flier, J. S. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0395 · Cited by 5,522
Mechanisms linking obesity to insulin resistance and type 2 diabetes
Kahn, S. E., Hull, R. L., & Utzschneider, K. M. (2006) · Nature · doi:10.1038/nature05482 · Cited by 5,448
Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice
Cani, P. D., Bibiloni, R., Knauf, C., Waget, A., Neyrinck, A. M., Delzenne, N. M., & Burcelin, R. (2008) · Diabetes · doi:10.2337/db07-1403 · Cited by 4,819
Inflammatory Mechanisms in Obesity
Gregor, M. F., & Hotamisligil, G. S. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101322 · Cited by 3,754
TLR4 links innate immunity and fatty acid-induced insulin resistance
Shi, H., Kokoeva, M. V., Inouye, K., Tzameli, I., Yin, H., & Flier, J. S. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28898 · Cited by 3,690
Complement: a key system for immune surveillance and homeostasis
Ricklin, D., Hajishengallis, G., Yang, K., & Lambris, J. D. (2010) · Nature Immunology · doi:10.1038/ni.1923 · Cited by 3,654
“, which has been associated with obesity and type II diabete”
Background
A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance
Newgard, C. B., An, J., Bain, J. R., Muehlbauer, M. J., Stevens, R. D., Lien, L. F., Haqq, A. M., Shah, S. H., Arlotto, M., Slentz, C. A., et al. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.02.002 · Cited by 3,165
Adipocytokines: mediators linking adipose tissue, inflammation and immunity
Tilg, H., & Moschen, A. R. (2006) · Nature reviews. Immunology · doi:10.1038/nri1937 · Cited by 3,272
Cytokines sing the blues: inflammation and the pathogenesis of depression
Raison, C. L., Capuron, L., & Miller, A. H. (2006) · Trends in Immunology · doi:10.1016/j.it.2005.11.006 · Cited by 3,009
Gut Microbiota in Human Adults with Type 2 Diabetes Differs from Non-Diabetic Adults
Larsen, N., Vogensen, F. K., van den Berg, F. W. J., Nielsen, D. S., Andreasen, A. S., Pedersen, B. K., Al-Soud, W. A., Sørensen, S. J., Hansen, L. H., & Jakobsen, M. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009085 · Cited by 2,952
Macrophages, inflammation, and insulin resistance
Olefsky, J. M., & Glass, C. K. (2010) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021909-135846 · Cited by 2,733
Chemical Chaperones Reduce ER Stress and Restore Glucose Homeostasis in a Mouse Model of Type 2 Diabetes
Özcan, U., Yilmaz, E., Özcan, L., Furuhashi, M., Vaillancourt, E., Smith, R. O., Görgün, C. Z., & Hotamisligil, G. S. (2006) · Science · doi:10.1126/science.1128294 · Cited by 2,413
Muscle as an Endocrine Organ: Focus on Muscle-Derived Interleukin-6
Pedersen, B. K., & Febbraio, M. A. (2008) · Physiological Reviews · doi:10.1152/physrev.90100.2007 · Cited by 2,388
The Metabolic Syndrome
Cornier, M.-A., Dabelea, D., Hernandez, T. L., Lindstrom, R. C., Steig, A. J., Stob, N. R., Van Pelt, R. E., Wang, H., & Eckel, R. H. (2008) · Endocrine Reviews · doi:10.1210/er.2008-0024 · Cited by 2,162
Fat and Beyond: The Diverse Biology of PPARγ
Tontonoz, P., & Spiegelman, B. M. (2008) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.77.061307.091829 · Cited by 2,085
Recent advances in the relationship between obesity, inflammation, and insulin resistance.
Bastard, J., Maachi, M., Lagathu, C., Kim, M. J., Caron, M., Vidal, H., Capeau, J., & Fève, B. (2006) · PubMed · Cited by 2,090
Insulin Resistance and the Polycystic Ovary Syndrome Revisited: An Update on Mechanisms and Implications
Diamanti-Kandarakis, E., & Dunaif, A. (2012) · Endocrine Reviews · doi:10.1210/er.2011-1034 · Cited by 1,947
Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia
Cani, P. D., Neyrinck, A. M., Fava, F., Knauf, C., Burcelin, R., Tuohy, K. M., Gibson, G. R., & Delzenne, N. M. (2007) · Diabetologia · doi:10.1007/s00125-007-0791-0 · Cited by 1,770
Reciprocal Relationships Between Insulin Resistance and Endothelial Dysfunction: Molecular and Pathophysiological Mechanisms
Kim, J.-A., Montagnani, M., Koh, K. K., & Quon, M. J. (2006) · Circulation · doi:10.1161/circulationaha.105.563213 · Cited by 1,652
CCR2 modulates inflammatory and metabolic effects of high-fat feeding
Weisberg, S. P., Hunter, D., Huber, R., Lemieux, J., Slaymaker, S., Vaddi, K., Charo, I., Leibel, R. L., & Jr., A. W. F. (2006) · Journal of Clinical Investigation · doi:10.1172/jci24335 · Cited by 1,497
CCR2 modulates inflammatory and metabolic effects of high-fat feeding
Weisberg, S. P. (2006) · Journal of Clinical Investigation · doi:10.1172/jci24335c1 · Cited by 1,425
Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions
Yamauchi, T., Nio, Y., Maki, T., Kobayashi, M., Takazawa, T., Iwabu, M., Okada-Iwabu, M., Kawamoto, S., Kubota, N., Kubota, T., et al. (2007) · Nature Medicine · doi:10.1038/nm1557 · Cited by 1,396
The role of estrogens in control of energy balance and glucose homeostasis
Mauvais-Jarvis, F., Clegg, D. J., & Hevener, A. L. (2013) · Endocrine Reviews · doi:10.1210/er.2012-1055 · Cited by 1,329
Macrophage-mediated inflammation in metabolic disease
Chawla, A., Nguyen, K. D., & Goh, Y. P. S. (2011) · Nature reviews. Immunology · doi:10.1038/nri3071 · Cited by 1,314
Relationship between Adipocyte Size and Adipokine Expression and Secretion
Skurk, T., Alberti-Huber, C., Herder, C., & Hauner, H. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-1055 · Cited by 1,288
Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans
Anderson, E. J., Lustig, M. E., Boyle, K. E., Woodlief, T. L., Kane, D. A., Lin, C.-T., Price, J. W., Kang, L., Rabinovitch, P. S., Szeto, H. H., et al. (2009) · Journal of Clinical Investigation · doi:10.1172/jci37048 · Cited by 1,253
Adipose Tissue Hypoxia in Obesity and Its Impact on Adipocytokine Dysregulation
Hosogai, N., Fukuhara, A., Oshima, K., Miyata, Y., Tanaka, S., Segawa, K., Furukawa, S., Tochino, Y., Komuro, R., Matsuda, M., et al. (2007) · Diabetes · doi:10.2337/db06-0911 · Cited by 1,257
Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota
Chang, C., Lin, C.-S., Lu, C., Martel, J., Ko, Y., Ojcius, D. M., Tseng, S., Wu, T.-R., Chen, Y. M., Young, J. D., et al. (2015) · Nature Communications · doi:10.1038/ncomms8489 · Cited by 1,254
Osteoarthritis: toward a comprehensive understanding of pathological mechanism
Chen, D., Shen, J., Zhao, W., Wang, T., Han, L., Hamilton, J. L., & Im, H. (2017) · Bone Research · doi:10.1038/boneres.2016.44 · Cited by 1,221
Resolvin E1 and protectin D1 activate inflammation-resolution programmes
Schwab, J. M., Chiang, N., Arita, M., & Serhan, C. N. (2007) · Nature · doi:10.1038/nature05877 · Cited by 1,219
High Fat Diet-Induced Gut Microbiota Exacerbates Inflammation and Obesity in Mice via the TLR4 Signaling Pathway
Kim, K., Gu, W., Lee, I., Joh, E., & Kim, D. (2012) · PLoS ONE · doi:10.1371/journal.pone.0047713 · Cited by 1,228
Molecular and metabolic mechanisms of insulin resistance and β-cell failure in type 2 diabetes
Muoio, D. M., & Newgard, C. B. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2327 · Cited by 1,177
A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice
Anhê, F. F., Roy, D., Pilon, G., Dudonné, S., Matamoros, S., Varin, T. V., Garofalo, C., Moine, Q., Desjardins, Y., Levy, E., et al. (2015) · Gut · doi:10.1136/gutjnl-2014-307142 · Cited by 1,137
Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation
Purushotham, A., Schug, T. T., Xu, Q., Surapureddi, S., Guo, X., & Li, X. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.02.006 · Cited by 1,003
Leptin and Obesity: Role and clinical implication.
Obradovic, M., Sudar-Milovanovic, E., Soskic, S., Essack, M., Arya, S., Stewart, A. J., Gojobori, T., & Isenovic, E. R. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.585887 · Cited by 1,121
Disordered lipid metabolism and the pathogenesis of insulin resistance.
Savage, D. B., Petersen, K. F., & Shulman, G. I. (2007) · Physiological Reviews · doi:10.1152/physrev.00024.2006 · Cited by 1,107
Insulin Resistance: From Mechanisms to Therapeutic Strategies
Lee, S.-H., Park, S., & Choi, C. S. (2021) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2021.0280 · Cited by 1,248
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
Pro-inflammatory cytokines: The link between obesity and osteoarthritis
Wang, T., & He, C. (2018) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2018.10.002 · Cited by 1,034
Interactions between gut microbiota, host genetics and diet relevant to development of metabolic syndromes in mice
Zhang, C., Zhang, M., Wang, S., Han, R., Cao, Y., Hua, W., Mao, Y., Zhang, X., Pang, X., Wei, C., et al. (2010) · The ISME Journal · doi:10.1038/ismej.2009.112 · Cited by 1,024
Nutrient sensing and inflammation in metabolic diseases
Hotamisligil, G. S., & Erbay, E. (2008) · Nature Reviews Immunology · doi:10.1038/nri2449 · Cited by 1,040
Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders
Choe, S. S., Huh, J. Y., Hwang, I. J., Kim, J. I., & Kim, J. B. (2016) · Frontiers in Endocrinology · doi:10.3389/fendo.2016.00030 · Cited by 1,206
A Subpopulation of Macrophages Infiltrates Hypertrophic Adipose Tissue and Is Activated by Free Fatty Acids via Toll-like Receptors 2 and 4 and JNK-dependent Pathways
Nguyen, M. T. A., Favelyukis, S., Nguyen, A.-K., Reichart, D., Scott, P. A., Jenn, A., Liu-Bryan, R., Glass, C. K., Neels, J. G., & Olefsky, J. M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m706762200 · Cited by 1,035
Mechanism linking diabetes mellitus and obesity
AlGoblan, A., Al-Alfi, M. A., & Khan, M. I. (2014) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s67400 · Cited by 1,108
Inflammation and immunity in the pathogenesis of pulmonary arterial hypertension
Rabinovitch, M., Guignabert, C., Humbert, M., & Nicolls, M. R. (2014) · Circulation Research · doi:10.1161/circresaha.113.301141 · Cited by 1,029
Uric Acid: The Oxidant-Antioxidant Paradox
Sautin, Y. Y., & Johnson, R. J. (2008) · Nucleosides Nucleotides & Nucleic Acids · doi:10.1080/15257770802138558 · Cited by 1,029
The role of the gut microbiota in energy metabolism and metabolic disease
Cani, P., & Delzenne, N. (2009) · Current Pharmaceutical Design · doi:10.2174/138161209788168164 · Cited by 974
Visfatin, an Adipocytokine with Proinflammatory and Immunomodulating Properties
Moschen, A. R., Kaser, A., Enrich, B., Mosheimer, B. A., Theurl, M., Niederegger, H., & Tilg, H. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.3.1748 · Cited by 957
Overexpression of Monocyte Chemoattractant Protein-1 in Adipose Tissues Causes Macrophage Recruitment and Insulin Resistance
Kamei, N., Tobe, K., Suzuki, R., Ohsugi, M., Watanabe, T., Kubota, N., Ohtsuka-Kowatari, N., Kumagai, K., Sakamoto, K. Q., Kobayashi, M., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m601284200 · Cited by 916
Diabetic Nephropathy: Challenges in Pathogenesis, Diagnosis, and Treatment
Samsu, N. (2021) · BioMed Research International · doi:10.1155/2021/1497449 · Cited by 1,001
Chemerin, a Novel Adipokine That Regulates Adipogenesis and Adipocyte Metabolism
Goralski, K. B., McCarthy, T. C., Hanniman, E. A., Zabel, B. A., Butcher, E. C., Parlee, S. D., Muruganandan, S., & Sinal, C. J. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700793200 · Cited by 867
Ceramides in insulin resistance and lipotoxicity
Summers, S. A. (2005) · Progress in Lipid Research · doi:10.1016/j.plipres.2005.11.002 · Cited by 866
Akkermansia muciniphila-derived extracellular vesicles influence gut permeability through the regulation of tight junctions
Chelakkot, C., Choi, Y., Kim, D., Park, H. T., Ghim, J., Kwon, Y., Jeon, J., Kim, M.-S., Jee, Y., Gho, Y. S., et al. (2018) · Experimental & Molecular Medicine · doi:10.1038/emm.2017.282 · Cited by 872
Animal models of obesity and diabetes mellitus
Kleinert, M., Clemmensen, C., Hofmann, S. M., Moore, M. C., Renner, S., Woods, S. C., Huypens, P., Beckers, J., de Angelis, M. H., Schürmann, A., et al. (2018) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.161 · Cited by 893
The gut microbiota and obesity: from correlation to causality
Zhao, L. (2013) · Nature Reviews Microbiology · doi:10.1038/nrmicro3089 · Cited by 860
The tumour microenvironment as a target for chemoprevention
Albini, A., & Sporn, M. B. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2067 · Cited by 828
Reactive oxygen species in health and disease
Alfadda, A. A., & Sallam, R. M. (2012) · Journal of Biomedicine and Biotechnology · doi:10.1155/2012/936486 · Cited by 824
Metabolic Dysfunction Drives a Mechanistically Distinct Proinflammatory Phenotype in Adipose Tissue Macrophages
Kratz, M., Coats, B. R., Hisert, K. B., Hagman, D. K., Mutskov, V. J., Peris, E., Schoenfelt, K. Q., Kuzma, J. N., Larson, I. A., Billing, P. S., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.08.010 · Cited by 866
Inflammation: The Common Pathway of Stress-Related Diseases
Liu, Y.-Z., Wang, Y.-X., & Jiang, C.-L. (2017) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2017.00316 · Cited by 800
Human blood vessel organoids as a model of diabetic vasculopathy
Wimmer, R. A., Leopoldi, A., Aichinger, M., Wick, N., Hantusch, B., Novatchkova, M., Taubenschmid, J., Hämmerle, M., Esk, C., Bagley, J. A., et al. (2019) · Nature · doi:10.1038/s41586-018-0858-8 · Cited by 803
Adverse effects of the classic antioxidant uric acid in adipocytes: NADPH oxidase-mediated oxidative/nitrosative stress
Sautin, Y. Y., Nakagawa, T., Zharikov, S. I., & Johnson, R. J. (2007) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00600.2006 · Cited by 799
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
Increased Number of Islet-Associated Macrophages in Type 2 Diabetes
Ehses, J. A., Perren, A. A., Eppler, E., Ribaux, P., Pospisilik, J. A., Maor-Cahn, R., Guéripel, X., Ellingsgaard, H., Schneider, M. K. J., Biollaz, G., et al. (2007) · Diabetes · doi:10.2337/db06-1650 · Cited by 804
Mechanisms of obesity-associated insulin resistance: many choices on the menuPreprint
Qatanani, M., & Lazar, M. A. (2007) · Genes & Development · doi:10.1101/gad.1550907 · Cited by 797
Glycogen synthase kinase-3 (GSK3): Inflammation, diseases, and therapeutics
Jope, R. S., Yuskaitis, C. J., & Beurel, E. (2007) · Neurochemical Research · doi:10.1007/s11064-006-9128-5 · Cited by 774
How might contact with nature promote human health? Promising mechanisms and a possible central pathway
Kuo, M. (2015) · Frontiers in Psychology · doi:10.3389/fpsyg.2015.01093 · Cited by 900
Effects of obesity on bone metabolism
Cao, J. (2011) · Journal of Orthopaedic Surgery and Research · doi:10.1186/1749-799x-6-30 · Cited by 798
Type 2 diabetes mellitus, oxidative stress and inflammation: examining the links.
Oguntibeju, O. O. (2019) · Europe PMC (PubMed Central) · Cited by 758
The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome
Petersen, K. F., Dufour, S., Savage, D. B., Bilz, S., Solomon, G., Yonemitsu, S., Cline, G. W., Befroy, D., Zemany, L., Kahn, B. B., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705408104 · Cited by 759
A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity
Okada-Iwabu, M., Yamauchi, T., Iwabu, M., Honma, T., Hamagami, K.-I., Matsuda, K., Yamaguchi, M., Tanabe, H., Kimura-Someya, T., Shirouzu, M., et al. (2013) · Nature · doi:10.1038/nature12656 · Cited by 757
Diabetic Retinopathy
Antonetti, D. A., Barber, A. J., Bronson, S. K., Freeman, W. M., Gardner, T. W., Jefferson, L. S., KESTER, M. A., Kimball, S. R., Krady, J. K., LaNoue, K. F., et al. (2006) · Diabetes · doi:10.2337/db05-1635 · Cited by 758
Angiogenesis modulates adipogenesis and obesity
Cao, Y. (2007) · Journal of Clinical Investigation · doi:10.1172/jci32239 · Cited by 736
The wolf in sheep's clothing: the role of interleukin-6 in immunity, inflammation and cancer
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Authors: Wellen, K. E., & Hotamisligil, G. S.
Affiliations: Harvard University (US)
ORCID: Wellen, Kathryn E.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2005-05-02
Volume: 115
Issue: 5
Pages: 1111-1119
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci25102
PMC: PMC1087185
OpenAlex: W2064119981
Cited by: 4,143
References: 118
Citations by year: 2026: 76 · 2025: 104 · 2024: 92 · 2023: 130 · 2022: 177 · 2021: 169 · 2020: 209 · 2019: 221 · 2018: 233 · 2017: 193 · 2016: 215 · 2015: 226 · 2014: 239 · 2013: 276 · 2012: 264
FWCI: 138.15
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: American Diabetes Association
National Institutes of Health
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 › Immune cells in cancer
Keywords: obesity-associated inflammation, low-grade inflammation, type 2 diabetes, insulin signaling, stress response, innate immunity, innate lymphoid cells, Th17 cells, Th1 cells, Th2 cells, regulatory T cells, Treg cell function, Treg cell homeostasis
MeSH terms: Animals, Diabetes Mellitus, Humans, Inflammation, Insulin Resistance, Macrophages, Obesity, Stress, Physiological, Adipocytes

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