Adipokines in inflammation and metabolic disease

Ouchi, Noriyuki; Parker, Jennifer L.; Lugus, Jesse J.; Walsh, Kenneth

doi:10.1038/nri2921

Cited by 4,625Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismCardiovascular Disease and Adiposity

Adipokines in inflammation and metabolic disease

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Ouchi, Noriyuki, Parker, Jennifer L., Lugus, Jesse J., Walsh, Kenneth·2011·Nature Reviews Immunology

DOI 10.1038/nri2921PMC PMC3518031

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Abstract

The worldwide epidemic of obesity has brought considerable attention to research aimed at understanding the biology of adipocytes (fat cells) and the events occurring in adipose tissue (fat) and in the bodies of obese individuals. Accumulating evidence indicates that obesity causes chronic low-grade inflammation and that this contributes to systemic metabolic dysfunction that is associated with obesity-linked disorders. Adipose tissue functions as a key endocrine organ by releasing multiple bioactive substances, known as adipose-derived secreted factors or adipokines, that have pro-inflammatory or anti-inflammatory activities. Dysregulated production or secretion of these adipokines owing to adipose tissue dysfunction can contribute to the pathogenesis of obesity-linked complications. In this Review, we focus on the role of adipokines in inflammatory responses and discuss their potential as regulators of metabolic function.

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Increased leptin levels have been found in the obese population, inducing a leptin-resistance state, accompanied by increased ROS, TNF-α, IL-6 and chemokine ligands.
“Increased leptin levels have been found in the obese population, inducing a leptin-resistance state, accompanied by increased ROS, TNF-α, IL-6 and chemokine ligands.”
From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [216]
The Leptin section reports that obese individuals have high blood leptin levels without the expected anorexic response, indicating leptin resistance. It also says leptin stimulates ROS, TNF, IL-6 and CC-chemokine ligand production in specified immune cells. It does not establish that increased leptin causes resistance or that all those inflammatory products are elevated alongside resistance in obese people. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Leptin augments Th1 cytokines IL-2 and IFN-γ while suppressing Th2 cytokine IL-4.
“Additionally, it augments Th1 cytokines IL-2 and IFN-γ while suppressing Th2 cytokine IL-4 [216].”
From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [216]
In obesity, adiponectin levels are found to be reduced, given that its expression is inhibited by hypoxia, oxidative stress, insulin resistance, TNF-α, IL-6, 'catecholamine resistance', fetuin A, and SeP.
“In obesity, adiponectin levels are found to be reduced [216], given that its expression is inhibited by hypoxia, oxidative stress [228], insulin resistance [229], TNF-α, IL-6 [229], “catecholamine resistance” [239], fetuin A [148], and SeP [136].”
From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [216]
In obesity, adipose tissue macrophages change phenotype from M2 to M1.
“In the context of obesity, adipose tissue macrophages (ATM) change their phenotype from M2 to M1.”
From Sarcopenic obesity: epidemiology, pathophysiology, cardiovascular disease, mortality, and management (2023) · cites this paper as [19]
By acting on white adipocyte mass, mitochondrial uncouplers could protect against diabetes.
“By acting on white adipocyte mass, mitochondrial uncouplers could protect against diabetes, as limiting hyperaccumulation of triacyglycerol (TAG) in these cells might limit organelle stress [91,273,274,275] and modifications in the expression pattern of genes encoding adipokines, which are known to communicate the level of adiposity to other organs [221,276].”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [276]

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Weight loss reduces interleukin-18 levels in obese women
Esposito, K., Pontillo, A., Ciotola, M., Di Palo, C., Grella, E., Nicoletti, G., & Giugliano, D. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.8.8781 · Cited by 254 · see citing works
Leptin Indirectly Activates Human Neutrophils via Induction of TNF-α
Zarkesh‐Esfahani, S. H., Pockley, A. G., Wu, Z., Hellewell, P. G., Weetman, A. P., & Ross, R. J. M. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.3.1809 · Cited by 243 · see citing works
Exacerbation of heart failure in adiponectin-deficient mice due to impaired regulation of AMPK and glucose metabolism
LIAO, Y., TAKASHIMA, S., MAEDA, N., OUCHI, N., KOMAMURA, K., SHIMOMURA, I., HORI, M., MATSUZAWA, Y., FUNAHASHI, T., & KITAKAZE, M. (2005) · Cardiovascular Research · doi:10.1016/j.cardiores.2005.04.018 · Cited by 236 · see citing works
Self-citation
Reduction of Elevated Serum Retinol Binding Protein in Obese Children by Lifestyle Intervention: Association with Subclinical Inflammation
Balagopal, P., Graham, T. E., Kahn, B. B., Altomare, A., Funanage, V. L., & George, D. E. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-2712 · Cited by 234 · see citing works
Macrophage-derived human resistin exacerbates adipose tissue inflammation and insulin resistance in mice
Qatanani, M., Szwergold, N. R., Greaves, D. R., Ahima, R. S., & Lazar, M. A. (2009) · Journal of Clinical Investigation · doi:10.1172/jci37273 · Cited by 229 · see citing works
Periadventitial Adipose Tissue Plays a Critical Role in Vascular Remodeling
Takaoka, M., Nagata, D., Kihara, S., Shimomura, I., Kimura, Y., Tabata, Y., Saito, Y., Nagai, R., & Sata, M. (2009) · Circulation Research · doi:10.1161/circresaha.109.199653 · Cited by 217 · see citing works
Adiponectin protects against the development of systolic dysfunction following myocardial infarction
Shibata, R., Izumiya, Y., Sato, K., Papanicolaou, K. N., Kihara, S., Colucci, W. S., Sam, F., Ouchi, N., & Walsh, K. X. (2007) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2007.03.808 · Cited by 213 · see citing works
Self-citation
Adiponectin Prevents Cerebral Ischemic Injury Through Endothelial Nitric Oxide Synthase–Dependent Mechanisms
Nishimura, M., Izumiya, Y., Higuchi, A., Shibata, R., Qiu, J., Kudo, C., Shin, H. K., Moskowitz, M. A., & Ouchi, N. (2007) · Circulation · doi:10.1161/circulationaha.107.725044 · Cited by 207 · see citing works
Self-citation
Lipocalin-2 Deficiency Impairs Thermogenesis and Potentiates Diet-Induced Insulin Resistance in Mice
Guo, H., Jin, D., Zhang, Y., Wright, W. S., Bazuine, M., Brockman, D. A., Bernlohr, D., & Chen, X. (2010) · Diabetes · doi:10.2337/db09-1735 · Cited by 206 · see citing works
Adiponectin Inhibits the Production of CXC Receptor 3 Chemokine Ligands in Macrophages and Reduces T-Lymphocyte Recruitment in Atherogenesis
Okamoto, Y., Folco, E. J. E., Minami, M., Wara, A. K., Feinberg, M. W., Sukhova, G. K., Colvin, R. A., Kihara, S., Funahashi, T., Luster, A. D., et al. (2007) · Circulation Research · doi:10.1161/circresaha.107.164988 · Cited by 202 · see citing works
Increased adipose tissue expression of lipocalin-2 in obesity is related to inflammation and matrix metalloproteinase-2 and metalloproteinase-9 activities in humans
Catalán, V., Gómez‐Ambrosi, J., Rodrı́guez, A., Ramírez, B., Silva, C., Rotellar, F., Gil, M. J. C., Cienfuegos, J. A., Salvador, J., & Frühbeck, G. (2009) · Journal of Molecular Medicine · doi:10.1007/s00109-009-0486-8 · Cited by 190 · see citing works
CXC Ligand 5 Is an Adipose-Tissue Derived Factor that Links Obesity to Insulin Resistance
Carine Chavey, A., Lazennec, G., Lagarrigue, S., Clapé, C., Iankova, I., Teyssier, J., Annicotte, J., Schmidt, J., Mataki, C., Yamamoto, H., et al. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.03.002 · Cited by 182 · see citing works
Interleukin-6 does/does not have a beneficial role in insulin sensitivity and glucose homeostasis
Pedersen, B. K., & Febbraio, M. A. (2006) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01208.2006 · Cited by 177 · see citing works
Adiponectin improves endothelial function in hyperlipidemic rats by reducing oxidative/nitrative stress and differential regulation of eNOS/iNOS activity
Li, R., Wang, W., Zhang, H., Yang, X., Fan, Q., Christopher, T. A., Lopez, B. L., Tao, L., Goldstein, B. J., Gao, F., et al. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00462.2007 · Cited by 169 · see citing works
Adiponectin and Functional Adiponectin Receptor 1 Are Expressed by Airway Epithelial Cells in Chronic Obstructive Pulmonary Disease
Miller, M., Cho, J. Y., Pham, A. K., Ramsdell, J., & Broide, D. H. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.182.1.684 · Cited by 163 · see citing works
Loss of Resistin Improves Glucose Homeostasis in Leptin Deficiency
Qi, Y., Nie, Z., Lee, Y.-S., Singhal, N. S., Scherer, P. E., Lazar, M. A., & Ahima, R. S. (2006) · Diabetes · doi:10.2337/db05-0615 · Cited by 156 · see citing works
IL-1β-Specific Up-Regulation of Neutrophil Gelatinase-Associated Lipocalin Is Controlled by IκB-ζ
Cowland, J. B., Muta, T., & Borregaard, N. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.9.5559 · Cited by 151 · see citing works
Monocyte Chemoattractant Protein-1 Deficiency Fails to Restrain Macrophage Infiltration Into Adipose Tissue
Kirk, E. A., Sagawa, Z. K., McDonald, T. O., O'Brien, K. D., & Heinecke, J. W. (2008) · Diabetes · doi:10.2337/db07-1061 · Cited by 149 · see citing works
Alveolar macrophage activation and an emphysema-like phenotype in adiponectin-deficient mice
Summer, R. S., Little, F. F., Ouchi, N., Takemura, Y., Aprahamian, T. R., Dwyer, D. F., Fitzsimmons, K. M., Suki, B., Parameswaran, H., Fine, A., et al. (2008) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00397.2007 · Cited by 144 · see citing works
Self-citation
Circulating visfatin level is correlated with inflammation, but not with insulin resistance
Oki, K., Yamane, K., Kamei, N., Nojima, H., & Kohno, N. (2007) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2007.02966.x · Cited by 136 · see citing works
Inhibition of CCR2 Ameliorates Insulin Resistance and Hepatic Steatosis in db/db Mice
Tamura, Y., Sugimoto, M., Murayama, T., Ueda, Y., Kanamori, H., Ono, K., Ariyasu, H., Akamizu, T., Kita, T., Yokode, M., et al. (2008) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.108.168633 · Cited by 135 · see citing works
Vaspin and visfatin/Nampt are interesting interrelated adipokines playing a role in the pathogenesis of type 2 diabetes mellitus
EL-Mesallamy, H. O., Kassem, D. H., El‐Demerdash, E., & Amin, A. I. (2010) · Metabolism · doi:10.1016/j.metabol.2010.04.008 · Cited by 134 · see citing works
Leptin enhances CC-chemokine ligand expression in cultured murine macrophage
Kiguchi, N., Maeda, T., Kobayashi, Y., Fukazawa, Y., & Kishioka, S. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.04.121 · Cited by 127 · see citing works
Retinol‐binding protein‐4 attenuates insulin‐induced phosphorylation of IRS1 and ERK1/2 in primary human adipocytes
Öst, A., Danielsson, A., Lidén, M., Eriksson, U., Nyström, F. H., & Strålfors, P. (2007) · The FASEB Journal · doi:10.1096/fj.07-8173com · Cited by 126 · see citing works
Caloric Restriction Stimulates Revascularization in Response to Ischemia via Adiponectin-mediated Activation of Endothelial Nitric-oxide Synthase
Kondo, M., Shibata, R., Miura, R., Shimano, M., Kondo, K., Li, P., Ohashi, T., Kihara, S., Maeda, N., Walsh, K., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m805301200 · Cited by 124 · see citing works
Self-citation
Associations among plasma adiponectin, hypertension, left ventricular diastolic function and left ventricular mass index
Hong, S. J., Park, C. G., Seo, H. S., Oh, D. J., & Ro, Y. M. (2004) · Blood Pressure · doi:10.1080/08037050410021397 · Cited by 121 · see citing works
Deficiency of Adiponectin Receptor 2 Reduces Diet-Induced Insulin Resistance but Promotes Type 2 Diabetes
Liu, Y., Michael, M. D., Kash, S. F., Bensch, W. R., Monia, B. P., Murray, S. F., Otto, K. A., Syed, S. K., Bhanot, S., Sloop, K. W., et al. (2006) · Endocrinology · doi:10.1210/en.2006-0708 · Cited by 113 · see citing works
Adiponectin deficiency: a model of pulmonary hypertension associated with pulmonary vascular disease
Summer, R. S., Fiack, C. A., Ikeda, Y., Sato, K., Dwyer, D. F., Ouchi, N., Fine, A., Farber, H. W., & Walsh, K. (2009) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.90599.2008 · Cited by 113 · see citing works
Self-citation
A Predominant Role for Parenchymal c-Jun Amino Terminal Kinase (JNK) in the Regulation of Systemic Insulin Sensitivity
Vallerie, S. N., Furuhashi, M., Fucho, R., & Hotamışlıgil, G. S. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003151 · Cited by 110 · see citing works
Evidence That Kidney Function but Not Type 2 Diabetes Determines Retinol-Binding Protein 4 Serum Levels
Henze, A., Frey, S. K., Raila, J., Tepel, M., Scholze, A., Pfeiffer, A. F. H., Weickert, M. O., Spranger, J., & Schweigert�, F. J. (2008) · Diabetes · doi:10.2337/db08-0866 · Cited by 109 · see citing works
Effects of TNF-α neutralization on adipocytokines and skeletal muscle adiposity in the metabolic syndrome
Lo, J., Bernstein, L. E., Hron, B. M., Torriani, M., Jackson, M. B., Ahima, R. S., & Grinspoon, S. K. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00089.2007 · Cited by 106 · see citing works
The Peroxisome Proliferator-Activated Receptor γ Agonist Rosiglitazone Ameliorates Murine Lupus by Induction of Adiponectin
Aprahamian, T. R., Bonegio, R. G. B., Richez, C., Yasuda, K., Chiang, L.-K., Sato, K., Walsh, K. X., & Rifkin, I. R. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.182.1.340 · Cited by 100 · see citing works
Self-citation
Effect of Etanercept on Insulin Sensitivity in Nine Patients with Psoriasis
Marra, M., Campanati, A., Testa, R., Sirolla, C., Bonfigli, A. R., Franceschi, C., Marchegiani, F., & Offidani, A. (2007) · International Journal of Immunopathology and Pharmacology · doi:10.1177/039463200702000408 · Cited by 98 · see citing works
Decreased clearance of serum retinol-binding protein and elevated levels of transthyretin in insulin-resistantob/obmice
Mody, N., Graham, T. E., Tsuji, Y., Yang, Q., & Kahn, B. B. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00521.2007 · Cited by 94 · see citing works
The pro-inflammatory cytokine IL-18 is expressed in human adipose tissue and strongly upregulated by TNFα in human adipocytes
Wood, I. S., Wang, B., Jenkins, J. R., & Trayhurn, P. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.09.068 · Cited by 94 · see citing works
Adiponectin Deficiency, Diastolic Dysfunction, and Diastolic Heart Failure
Sam, F., Duhaney, T.-A. S., Sato, K., Wilson, R. M., Ohashi, K., Sono-Romanelli, S., Higuchi, A., Silva, D. S. D., Qin, F., Walsh, K., et al. (2009) · Endocrinology · doi:10.1210/en.2009-0806 · Cited by 90 · see citing works
Self-citation
Adiponectin Promotes Revascularization of Ischemic Muscle through a Cyclooxygenase 2-Dependent Mechanism
Ohashi, K., Ouchi, N., Sato, K., Higuchi, A., Ishikawa, T., Herschman, H. R., Kihara, S., & Walsh, K. X. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00126-09 · Cited by 83 · see citing works
Self-citation
Adiponectin Deficiency Limits Tumor Vascularization in the MMTV-PyV-mT Mouse Model of Mammary Cancer
Denzel, M. S., Hebbard, L., Shostak, G., Shapiro, L. S., Cardiff, R. D., & Ranscht, B. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-2661 · Cited by 83 · see citing works
COUNTERPOINT: INTERLEUKIN-6 DOES NOT HAVE A BENEFICIAL ROLE IN INSULIN SENSITIVITY AND GLUCOSE HOMEOSTASIS
Mooney, R. A. (2007) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01208a.2006 · Cited by 71 · see citing works
Plasma adiponectin and mortality in critically ill subjects with acute respiratory failure*
Walkey, A. J., Rice, T. W., Konter, J., Ouchi, N., Shibata, R., Walsh, K., deBoisblanc, B. P., & Summer, R. S. (2010) · Critical Care Medicine · doi:10.1097/ccm.0b013e3181fa0561 · Cited by 68 · see citing works
Self-citation
Lack of Association Between Adiponectin Levels and Atherosclerosis in Mice
Nawrocki, A. R., Hofmann, S. M., Teupser, D., Basford, J. E., Durand, J. L., Jelicks, L. A., Woo, C. W., Kuriakose, G., Factor, S. M., Tanowitz, H. B., et al. (2010) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.109.195826 · Cited by 63 · see citing works
Macrophages are Novel Sites of Expression and Regulation of Retinol Binding Protein-4 (RBP4)
Broch, M., Ramírez, R., Auguet, T., Alcaide, M. J., Aguilar, C., García‐España, A., & Richart, C. (2010) · Physiological Research · doi:10.33549/physiolres.931714 · Cited by 53 · see citing works
Impact of Adiponectin Deficiency on Pulmonary Responses to Acute Ozone Exposure in Mice
Zhu, M., Hug, C., Kasahara, D. I., Johnston, R. A., Williams, A. S., Verbout, N. G., Si, H., Jastrab, J. B., Srivastava, A., Williams, E. S., et al. (2009) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2009-0086oc · Cited by 42 · see citing works
Serum retinol binding protein 4 level is related with renal functions in Type 2 diabetes
Akbay, E., Muşlu, N., Nayır, E., Ozhan, O., & KIYKIM, A. A. (2010) · Journal of Endocrinological Investigation · doi:10.1007/bf03346678 · Cited by 41 · see citing works
IL-18 overexpression promotes vascular inflammation and remodeling in a rat model of metabolic syndrome
Tan, H., Liu, X., Bi, X., Xing, S., Li, L., Gong, H., Zhong, M., Wang, Z., Zhang, Y., & Zhang, W. (2009) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2009.07.053 · Cited by 40 · see citing works
Adiponectin ameliorates hypoxia-induced pulmonary arterial remodeling
Nakagawa, Y., Kishida, K., Kihara, S., Funahashi, T., & Shimomura, I. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.03.004 · Cited by 39 · see citing works

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Richness of human gut microbiome correlates with metabolic markers
Le Chatelier, E., Nielsen, T., Qin, J., Prifti, E., Hildebrand, F., Falony, G., Almeida, M., Arumugam, M., Batto, J.-M., Kennedy, S., et al. (2013) · Nature · doi:10.1038/nature12506 · Cited by 4,662 · see citing works
Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis
Gimbrone, M. A., & García‐Cardeña, G. (2016) · Circulation Research · doi:10.1161/circresaha.115.306301 · Cited by 3,554 · see citing works
Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies
Keum, N., & Giovannucci, E. L. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0189-8 · Cited by 2,690 · see citing works
Pathophysiology of human visceral obesity: an update
Tchernof, A., & Després, J.-P. (2013) · Physiological Reviews · doi:10.1152/physrev.00033.2011 · Cited by 2,583 · see citing works
The anti-inflammatory effects of exercise: Mechanisms and implications for the prevention and treatment of disease
Gleeson, M., Bishop, N. C., Stensel, D. J., Lindley, M. R., Mastana, S. S., & Nimmo, M. A. (2011) · Nature Reviews Immunology · doi:10.1038/nri3041 · Cited by 2,470 · see citing works
Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes
Esser, N., Legrand-Poels, S., Piette, J., Scheen, A. J., & Paquot, N. (2014) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2014.04.006 · Cited by 1,981 · see citing works
Obesity and Its Metabolic Complications: The Role of Adipokines and the Relationship between Obesity, Inflammation, Insulin Resistance, Dyslipidemia and Nonalcoholic Fatty Liver Disease
Jung, U. J., & Choi, M. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms15046184 · Cited by 1,898 · see citing works
Dietary intervention impact on gut microbial gene richness
Cotillard, A., Kennedy, S. P., Kong, L. C., Prifti, E., Pons, N., Le Chatelier, E., Almeida, M., Quinquis, B., Levenez, F., Galleron, N., et al. (2013) · Nature · doi:10.1038/nature12480 · Cited by 1,832 · see citing works
Mechanisms of physiological and pathological cardiac hypertrophy
Nakamura, M., & Sadoshima, J. (2018) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0007-y · Cited by 1,662 · see citing works
Visceral and ectopic fat, atherosclerosis, and cardiometabolic disease: a position statement
Neeland, I. J., Ross, R., Després, J.-P., Matsuzawa, Y., Yamashita, S., Shai, I., Seidell, J., Magni, P., Santos, R. D., Arsenault, B., et al. (2019) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(19)30084-1 · Cited by 1,603 · see citing works
The cellular and signaling networks linking the immune system and metabolism in disease
Osborn, O., & Olefsky, J. M. (2012) · Nature Medicine · doi:10.1038/nm.2627 · Cited by 1,551 · see citing works
Inflammation, Oxidative Stress, and Obesity
Fernández-Sánchez, A., Madrigal‐Santillán, E., Bautista, M., Esquivel-Soto, J., Morales‐González, Á., Esquivel-Chirino, C., Durante-Montiel, I., Sánchez-Rivera, G., Valadez-Vega, M. D. C., & Morales‐González, J. A. (2011) · International Journal of Molecular Sciences · doi:10.3390/ijms12053117 · Cited by 1,536 · see citing works
Hepatic stellate cells as key target in liver fibrosis
Higashi, T., Friedman, S. L., & Hoshida, Y. (2017) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2017.05.007 · Cited by 1,485 · see citing works
Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases
Incalza, M. A., D’Oria, R., Natalicchio, A., Perrini, S., Laviola, L., & Giorgino, F. (2017) · Vascular Pharmacology · doi:10.1016/j.vph.2017.05.005 · Cited by 1,375 · see citing works
Physical activity and depression: towards understanding the antidepressant mechanisms of physical activity
Kandola, A., Ashdown-Franks, G., Hendrikse, J., Sabiston, C. M., & Stubbs, B. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.09.040 · Cited by 1,309 · see citing works
Metabolic Regulation of T Lymphocytes
MacIver, N. J., Michalek, R. D., & Rathmell, J. C. (2013) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032712-095956 · Cited by 1,244 · see citing works
Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies
Manna, P., & Jain, S. K. (2015) · Metabolic Syndrome and Related Disorders · doi:10.1089/met.2015.0095 · Cited by 1,167 · see citing works
Obesity
González‐Muniesa, P., Martínez‐González, M. Á., Hu, F. B., Després, J., Matsuzawa, Y., Loos, R. J. F., Moreno, L. A., Bray, G. A., & Martínez, J. A. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.34 · Cited by 1,142 · see citing works
State of the art paper Biochemistry of adipose tissue: an endocrine organ
Coelho, M., Oliveira, T., & Fernandes, R. (2013) · Archives of Medical Science · doi:10.5114/aoms.2013.33181 · Cited by 1,125 · see citing works
Adipose Tissue in Obesity-Related Inflammation and Insulin Resistance: Cells, Cytokines, and Chemokines
Makki, K., Froguel, P., & Wolowczuk, I. (2013) · ISRN Inflammation · doi:10.1155/2013/139239 · Cited by 1,085 · see citing works
The vagus nerve and the inflammatory reflex – linking immunity and metabolism
Pavlov, V. A., & Tracey, K. J. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.189 · Cited by 1,040 · see citing works
Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis
Rolo, A. P., Teodoro, J. S., & Palmeira, C. M. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.10.003 · Cited by 955 · see citing works
Role of neuroinflammation in neurodegenerative diseases (Review)
Chen, W., Zhang, X., & Huang, W. (2016) · Molecular Medicine Reports · doi:10.3892/mmr.2016.4948 · Cited by 933 · see citing works
Global Impacts of Western Diet and Its Effects on Metabolism and Health: A Narrative Review
Clemente‐Suárez, V. J., Beltrán-Velasco, A. I., Redondo-Flórez, L., Martín-Rodríguez, A., & Tornero-Aguilera, J. F. (2023) · Nutrients · doi:10.3390/nu15122749 · Cited by 873 · see citing works
Targeting mitochondrial reactive oxygen species as novel therapy for inflammatory diseases and cancers
Li, X., Fang, P., Mai, J., Choi, E. T., Wang, H., & Yang, X. (2013) · Journal of Hematology & Oncology · doi:10.1186/1756-8722-6-19 · Cited by 810 · see citing works
Obesity and diabetes: the increased risk of cancer and cancer-related mortality
Gallagher, E. J., & LeRoith, D. (2015) · Physiological Reviews · doi:10.1152/physrev.00030.2014 · Cited by 806 · see citing works
Adipose tissue and adipocytes support tumorigenesis and metastasis
Nieman, K. M., Romero, I. L., Houten, B. V., & Lengyel, E. R. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2013.02.010 · Cited by 748 · see citing works
Signaling by IL-6 promotes alternative activation of macrophages to limit endotoxemia and obesity-associated resistance to insulin
Mauer, J., Chaurasia, B., Goldau, J., Vogt, M. C., Ruud, J., Nguyen, K. D., Theurich, S., Hausen, A. C., Schmitz, J., Brönneke, H. S., et al. (2014) · Nature Immunology · doi:10.1038/ni.2865 · Cited by 727 · see citing works
Obesity-related glomerulopathy: clinical and pathologic characteristics and pathogenesis
D’Agati, V. D., Chagnac, A., de Vries, A. P. J., Levi, M., Porrini, E., Herman‐Edelstein, M., & Praga, M. (2016) · Nature Reviews Nephrology · doi:10.1038/nrneph.2016.75 · Cited by 726 · see citing works
Cellular and molecular players in adipose tissue inflammation in the development of obesity-induced insulin resistance
Lee, B.-C., & Lee, J. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.05.017 · Cited by 697 · see citing works
Adipokines Mediate Inflammation and Insulin Resistance
Kwon, H., & Pessin, J. E. (2013) · Frontiers in Endocrinology · doi:10.3389/fendo.2013.00071 · Cited by 695 · see citing works
Circadian misalignment increases cardiovascular disease risk factors in humans
Morris, C. J., Purvis, T. E., Hu, K., & Scheer, F. A. J. L. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1516953113 · Cited by 691 · see citing works
Body Fat Distribution, Incident Cardiovascular Disease, Cancer, and All-Cause Mortality
Britton, K. A., Massaro, J. M., Murabito, J. M., Kreger, B. E., Hoffmann, U., & Fox, C. S. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.06.027 · Cited by 687 · see citing works
Obesity-Induced Changes in Adipose Tissue Microenvironment and Their Impact on Cardiovascular Disease
Fuster, J. J., Ouchi, N., Gokce, N., & Walsh, K. X. (2016) · Circulation Research · doi:10.1161/circresaha.115.306885 · Cited by 669 · see citing works
Self-citation
Adiposity and cancer risk: new mechanistic insights from epidemiology
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Authors: Ouchi, N., Parker, J. L., Lugus, J. J., & Walsh, K.
Affiliations: Nagoya University (JP)
Boston University (US)
Corresponding author: Walsh, Kenneth
ORCID: Ouchi, Noriyuki
Walsh, Kenneth
Venue: Nature Reviews Immunology
Publisher: Springer Science and Business Media LLC
Published: 2011-01-21
Volume: 11
Issue: 2
Pages: 85-97
ISSN: 1474-1733 (ISSN-L)
1474-1741
DOI: 10.1038/nri2921
PMC: PMC3518031
OpenAlex: W2088940658
Cited by: 4,625
References: 188
Citations by year: 2026: 294 · 2025: 311 · 2024: 301 · 2023: 326 · 2022: 363 · 2021: 358 · 2020: 370 · 2019: 371 · 2018: 286 · 2017: 335 · 2016: 279 · 2015: 270 · 2014: 264 · 2013: 250 · 2012: 171
FWCI: 27.15
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature reviews. Immunology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Institute on Aging (R01AG015052, R37AG015052, AG15052, AG34972, R01AG034972)
National Heart, Lung, and Blood Institute (HL81587, R01HL086785, P01HL081587, HL 86785)
Topics: Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
Keywords: adipokines, adipose tissue, obesity, low-grade inflammation, metabolic disorders, adipocytes, adipose tissue dysfunction, adipose tissue endocrine function, metabolic dysfunction
MeSH terms: Humans, Inflammation, Obesity, Adipokines

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