Obesity induces a phenotypic switch in adipose tissue macrophage polarization
Open accessAbstract
Adipose tissue macrophages (ATMs) infiltrate adipose tissue during obesity and contribute to insulin resistance. We hypothesized that macrophages migrating to adipose tissue upon high-fat feeding may differ from those that reside there under normal diet conditions. To this end, we found a novel F4/80(+)CD11c(+) population of ATMs in adipose tissue of obese mice that was not seen in lean mice. ATMs from lean mice expressed many genes characteristic of M2 or "alternatively activated" macrophages, including Ym1, arginase 1, and Il10. Diet-induced obesity decreased expression of these genes in ATMs while increasing expression of genes such as those encoding TNF-alpha and iNOS that are characteristic of M1 or "classically activated" macrophages. Interestingly, ATMs from obese C-C motif chemokine receptor 2-KO (Ccr2-KO) mice express M2 markers at levels similar to those from lean mice. The antiinflammatory cytokine IL-10, which was overexpressed in ATMs from lean mice, protected adipocytes from TNF-alpha-induced insulin resistance. Thus, diet-induced obesity leads to a shift in the activation state of ATMs from an M2-polarized state in lean animals that may protect adipocytes from inflammation to an M1 proinflammatory state that contributes to insulin resistance.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Obese ATMs produce high levels of TNFα, IL-6, and IL-1β, also elevated in insulin resistant individuals.
“These cells produce high levels of TNFα, IL-6, and IL-1β, all of which are also observed in increased levels of adipose tissue from insulin resistant individuals.”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [70]
In obesity, ATMs have a strongly polarized pro-inflammatory M1 phenotype.
“While the ATMs present in healthy lean adipose tissue are primarily of an M2 phenotype, those that accumulate in the adipose tissue during obesity have a strongly polarized pro-inflammatory, M1 phenotype [63,69–71].”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [70]
Two studies that investigated cellular markers of inflammation both reported an anti-inflammatory effect of vitamin D.
“However, two studies that investigated cellular markers of inflammation both reported an anti-inflammatory effect of vitamin D (747,748) .”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [747]
Devaraj et al. found significant inverse relationships between serum 25(OH)D3 and CRP concentration, monocyte NF-κB activation and TLR4 expression in pooled healthy subjects, type 1 diabetics and type 1 diabetics with microvascular complications.
“Using data pooled from thirty-six healthy subjects, twenty-four type 1 diabetics and twenty-six type 1 diabetics with microvascular complications, Devaraj et al. (747) found significant inverse relationships between serum 25(OH)D 3 and CRP concentration, monocyte NF-kB activation and TLR4 expression.”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [747]
These proinflammatory macrophages are implicated in the development of insulin resistance.
“Accordingly, because of their proinflammatory properties, these macrophages are implicated in the pathogenesis of insulin resistance (103, 105, 112, 113).”
From Insulin sensitivity: Modulation by nutrients and inflammation (2008) · cites this paper as [103]
The combination of microhypoxia and lipid overload triggers the recruitment of immune cells, such as macrophages in adipose tissue, and their activation.
“The combination of microhypoxia and lipid overload triggers the recruitment of immune cells, such as macrophages in the adipose tissue and their activation ([103](#B103), [129](#B129), [171](#B171)).”
From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [103]
Under stimulation by B cells, effector T cells and Th1 cells release cytokines such as interferon-γ to further stimulate activation of macrophages and induce a shift in macrophages from an M2-like phenotype to an M1-like phenotype.
“Under stimulation by B cells, effector T cells and Th1cells release cytokines such as interferon-γ to further stimulate activation of macrophages and induce a shift in macrophages from an M2-like phenotype to an M1-like phenotype.”
From The Vasculature in Prediabetes (2018) · cites this paper as [83]
In obese mice, a shift in the activation state of WAT macrophages from an M2 'alternatively activated' state to an M1 'pro-inflammatory state' was observed in response to diet-induced obesity.
“In obese mice, a shift in the activation state of WAT macrophages from an M2 'alternatively activated' state to an M1 'pro-inflammatory state' was observed in response to diet-induced obesity [47].”
From Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity (2008) · cites this paper as [47]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
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 · see citing works
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 · see citing works
The chemokine system in diverse forms of macrophage activation and polarization
MANTOVANI, A., SICA, A., SOZZANI, S., ALLAVENA, P., VECCHI, A., & LOCATI, M. (2004) · Trends in Immunology · doi:10.1016/j.it.2004.09.015 · Cited by 6,534 · see citing works
Alternative activation of macrophages
Gordon, S. (2003) · Nature Reviews Immunology · doi:10.1038/nri978 · Cited by 6,189 · see citing works
MANTOVANI, A., SOZZANI, S., LOCATI, M., ALLAVENA, P., & SICA, A. (2002) · Trends in Immunology · doi:10.1016/s1471-4906(02)02302-5 · Cited by 5,528 · see citing works
Monocyte and macrophage heterogeneity
Gordon, S., & Taylor, P. R. (2005) · Nature Reviews Immunology · doi:10.1038/nri1733 · Cited by 5,190 · see citing works
Inflammation and insulin resistance
Shoelson, S. E. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29069 · Cited by 4,769 · see citing works
Blood Monocytes Consist of Two Principal Subsets with Distinct Migratory Properties
Geissmann, F., Jung, S., & Littman, D. R. (2003) · Immunity · doi:10.1016/s1074-7613(03)00174-2 · Cited by 3,366 · see citing works
Kim, H. J., Park, S. Y., Choi, Y. J., Han, S. J., Lee, K. W., & Kim, D. J. (2013) · Hormone Research in Paediatrics · doi:10.1159/000348848 · Cited by 3,061 · see citing works
Kanda, H. (2006) · Journal of Clinical Investigation · doi:10.1172/jci26498 · Cited by 2,682 · see citing works
Regulation of immune responses by L-arginine metabolism
Bronte, V., & Zanovello, P. (2005) · Nature Reviews Immunology · doi:10.1038/nri1668 · Cited by 1,775 · see citing works
IKK-β links inflammation to obesity-induced insulin resistance
Arkan, M. C., Hevener, A. L., Greten, F. R., Maeda, S., Li, Z.-W., Long, J. M., Wynshaw-Boris, A., Poli, G., Olefsky, J., & Karin, M. (2005) · Nature Medicine · doi:10.1038/nm1185 · Cited by 1,773 · see citing works
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 · see citing works
CCR2 modulates inflammatory and metabolic effects of high-fat feeding
Weisberg, S. P. (2006) · Journal of Clinical Investigation · doi:10.1172/jci24335c1 · Cited by 1,424 · see citing works
Oxidative metabolism and PGC-1β attenuate macrophage-mediated inflammation
Vats, D., Mukundan, L., Odegaard, J. I., Zhang, L., Smith, K. L., Morel, C. R., Greaves, D. R., Murray, P. J., & Chawla, A. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.05.011 · Cited by 1,369 · see citing works
Lee, J. Y., Sohn, K. H., Rhee, S. H., & Hwang, D. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m011695200 · Cited by 1,299 · see citing works
Obesity and the role of adipose tissue in inflammation and metabolism
Greenberg, A. S., & Obin, M. S. (2006) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/83.2.461s · Cited by 1,271 · see citing works
Cancello, R., Henegar, C., Viguerie, N., Taleb, S., Poitou, C., Rouault, C., Coupaye, M., Pelloux, V., Hugol, D., Bouillot, J.-L., et al. (2005) · Diabetes · doi:10.2337/diabetes.54.8.2277 · Cited by 1,164 · see citing works
Subpopulations of Mouse Blood Monocytes Differ in Maturation Stage and Inflammatory Response
Sunderkötter, C., Nikolic, T., Dillon, M. J., van Rooijen, N., Stehling, M., Drevets, D. A., & Leenen, P. J. M. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.7.4410 · Cited by 1,124 · see citing works
Lumeng, C. N., DeYoung, S. M., Bodzin, J. L., & Saltiel, A. R. (2007) · Diabetes · doi:10.2337/db06-1076 · Cited by 1,016 · see citing works
Self-citationStout, R. D., Jiang, C., Matta, B., Tietzel, I., Watkins, S. K., & Suttles, J. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.1.342 · Cited by 968 · see citing works
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 918 · see citing works
Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1RA in human leukocytes
Wolf, A. M., Wolf, D. G. F., Rumpold, H. F., Enrich, B., & Tilg, H. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.08.145 · Cited by 821 · see citing works
Functional plasticity of macrophages: reversible adaptation to changing microenvironments
Stout, R. D., & Suttles, J. (2004) · Journal of Leukocyte Biology · doi:10.1189/jlb.0504272 · Cited by 751 · see citing works
CAP defines a second signalling pathway required for insulin-stimulated glucose transport
Baumann, C. A., Ribon, V., Kanzaki, M., Thurmond, D. C., Mora, S., Shigematsu, S., Bickel, P. E., Pessin, J. E., & Saltiel, A. R. (2000) · Nature · doi:10.1038/35025089 · Cited by 660 · see citing works
Self-citationCirculating Mononuclear Cells in the Obese Are in a Proinflammatory State
Ghanim, H., Aljada, A., Hofmeyer, D., Syed, T., Mohanty, P., & Dandona, P. (2004) · Circulation · doi:10.1161/01.cir.0000142055.53122.fa · Cited by 611 · see citing works
Cancello, R., Tordjman, J., Poitou, C., Guilhem, G., Bouillot, J. L., Hugol, D., Coussieu, C., Basdevant, A., Hen, A. B., Bedossa, P., et al. (2006) · Diabetes · doi:10.2337/db06-0133 · Cited by 607 · see citing works
Th1/Th2-Regulated Expression of Arginase Isoforms in Murine Macrophages and Dendritic Cells
Munder, M., Eichmann, K., Morán, J. M., Centeno, F., Soler, G., & Modolell, M. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.7.3771 · Cited by 561 · see citing works
Stephens, J. M., Lee, J., & Pilch, P. F. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.2.971 · Cited by 553 · see citing works
Differential Effects of Interleukin-6 and -10 on Skeletal Muscle and Liver Insulin Action In Vivo
Kim, H.-J., Higashimori, T., Park, S.-Y., Choi, H., Dong, J., Kim, Y.-J., Noh, H.-L., Cho, Y.-R., Cline, G., Kim, Y.-B., et al. (2004) · Diabetes · doi:10.2337/diabetes.53.4.1060 · Cited by 534 · see citing works
Migratory fate and differentiation of blood monocyte subsets
Tacke, F., & Randolph, G. J. (2006) · Immunobiology · doi:10.1016/j.imbio.2006.05.025 · Cited by 528 · see citing works
Interleukin-10 Signaling Blocks Inhibitor of κB Kinase Activity and Nuclear Factor κB DNA Binding
Schottelius, A. J. G., Mayo, M. W., Sartor, R. B., & Baldwin, A. S. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.45.31868 · Cited by 526 · see citing works
Inflamed fat: what starts the fire?
Neels, J. G. (2005) · Journal of Clinical Investigation · doi:10.1172/jci27280 · Cited by 463 · see citing works
Bruun, J. M., Helge, J. W., Richelsen, B., & Stallknecht, B. M. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00506.2005 · Cited by 431 · see citing works
Murray, P. J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500419102 · Cited by 394 · see citing works
Williams, L. M., Bradley, L., Smith, A. J., & Foxwell, B. M. J. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.1.567 · Cited by 394 · see citing works
Lumeng, C. N., Deyoung, S. M., & Saltiel, A. R. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00284.2006 · Cited by 359 · see citing works
Self-citationCX3CR1+ interstitial dendritic cells form a contiguous network throughout the entire kidney
Soos, T. J., Sims, T. N., Barisoni, L. M. C., Lin, K. L., Littman, D. R., Dustin, M. L., & Nelson, P. J. (2006) · Kidney International · doi:10.1038/sj.ki.5001567 · Cited by 309 · see citing works
Raes, G., Brys, L., Dahal, B. K., Brandt, J., Grooten, J., Brombacher, F., Vanham, G., Noël, W., Bogaert, P., Boonefaes, T., et al. (2004) · Journal of Leukocyte Biology · doi:10.1189/jlb.0304212 · Cited by 246 · see citing works
Interleukin‐10 suppression of myeloid cell activation — a continuing puzzle
Williams, L. M., Ricchetti, G., Sarma, U., Smallie, T., & Foxwell, B. M. J. (2004) · Immunology · doi:10.1111/j.1365-2567.2004.01988.x · Cited by 233 · see citing works
Dahlman, I. A., Kaaman, M., Olsson, T., Tan, G. D., Bickerton, A. S. T., Wåhlén, K., Andersson, J. S. O., Nordström, E. A., Blomqvist, L., Sjögren, A., et al. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-0369 · Cited by 207 · see citing works
Oberbach, A., Tönjes, A., Klöting, N., Faßhauer, M., Kratzsch, J., Busse, M. W., Paschke, R., Stümvoll, M., & Blüher, M. (2006) · European Journal of Endocrinology · doi:10.1530/eje.1.02127 · Cited by 199 · see citing works
Blüher, M., Faßhauer, M., Tönjes, A., Kratzsch, J., Schön, M., & Paschke, R. (2005) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-2005-872851 · Cited by 193 · see citing works
Katakura, T., Miyazaki, M., Kobayashi, M., Herndon, D. N., & Suzuki, F. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.3.1407 · Cited by 182 · see citing works
Claycombe, K., Harkins, J. M., Chung, Y.-J., Penner, K. M., Pestka, J. J., North, C. M., & Moustaïd‐Moussa, N. (2004) · Journal of Nutrition · doi:10.1093/jn/134.10.2673 · Cited by 169 · see citing works
Adipose tissue is a regulated source of interleukin-10
Juge-Aubry, C. E., Somm, E., Pernin, A., Alizadeh, N., Giusti, V., Dayer, J.-M., & Meier, C. A. (2005) · Cytokine · doi:10.1016/j.cyto.2004.10.017 · Cited by 144 · see citing works
Compartmentalization of the Exocyst Complex in Lipid Rafts Controls Glut4 Vesicle Tethering
Inoue, M., Chiang, S.-H., Chang, L. C., Chen, X., & Saltiel, A. R. (2006) · Molecular Biology of the Cell · doi:10.1091/mbc.e06-01-0030 · Cited by 126 · see citing works
Self-citationScarpelli, D., Cardellini, M., Andreozzi, F., Laratta, E., Hribal, M. L., Marini, M. A., Tassi, V., Lauro, R., Perticone, F., & Sesti, G. (2006) · Diabetes · doi:10.2337/db06-0047 · Cited by 111 · see citing works
Ginderachter, J. A. V., Meerschaut, S., Liu, Y., Brys, L., Groeve, K. D., Ghassabeh, G. H., Raes, G., & BAETSELIER, P. D. (2006) · Blood · doi:10.1182/blood-2005-09-3777 · Cited by 109 · see citing works
Zhou, J.-H., Broussard, S. R., Strle, K., Freund, G. G., Johnson, R. W., Dantzer, R., & Kelley, K. W. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.8.4436 · Cited by 79 · see citing works
Decreased visceral adiposity accounts for leptin effect on hepatic but not peripheral insulin action
Barzilai, N., She, L., Liu, L., Wang, J., Hu, M., Vuguin, P. M., & Rossetti, L. (1999) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1999.277.2.e291 · Cited by 63 · see citing works
Dupasquier, M., Stoitzner, P., Wan, H., Cerqueira, D. I., van Oudenaren, A., Voerman, J. S. A., Denda‐Nagai, K., Irimura, T., Raes, G., Romani, N., et al. (2006) · Journal of Leukocyte Biology · doi:10.1189/jlb.1005564 · Cited by 62 · see citing works
Regulation of macrophage phenotype by long-term exposure to IL-10
Park‐Min, K., Antoniv, T. T., & Ivashkiv, L. B. (2005) · Immunobiology · doi:10.1016/j.imbio.2005.05.002 · Cited by 58 · see citing works
Adipose Tissue Metabolism and CD11b Expression on Monocytes in Obese Hypertensives
Boschmann, M., Engeli, S., Adams, F., Gorzelniak, K., Franke, G., Klaua, S., Kreuzberg, U., Luedtke, S., Kettritz, R., Sharma, A. M., et al. (2005) · Hypertension · doi:10.1161/01.hyp.0000171477.63859.b2 · Cited by 45 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Exploring the full spectrum of macrophage activation
Mosser, D. M., & Edwards, J. P. (2008) · Nature Reviews Immunology · doi:10.1038/nri2448 · Cited by 9,144 · see citing works
Macrophage plasticity and polarization: in vivo veritas
Sica, A., & Mantovani, A. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59643 · Cited by 6,335 · see citing works
Protective and pathogenic functions of macrophage subsets
Murray, P. J., & Wynn, T. A. (2011) · Nature Reviews Immunology · doi:10.1038/nri3073 · Cited by 5,269 · see citing works
Macrophage biology in development, homeostasis and disease
Wynn, T. A., Chawla, A., & Pollard, J. W. (2013) · Nature · doi:10.1038/nature12034 · Cited by 4,684 · see citing works
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
Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm
Biswas, S. K., & Mantovani, A. (2010) · Nature Immunology · doi:10.1038/ni.1937 · Cited by 3,840 · see citing works
Type 2 diabetes as an inflammatory disease
Donath, M. Y., & Shoelson, S. E. (2011) · Nature Reviews Immunology · doi:10.1038/nri2925 · Cited by 3,737 · see citing works
Mechanisms underlying inflammation in neurodegeneration
Glass, C. K., Saijo, K., Winner, B., Marchetto, M. C., & Gage, F. H. (2010) · Cell · doi:10.1016/j.cell.2010.02.016 · Cited by 3,580 · see citing works
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 · see citing works
The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance
Vandanmagsar, B., Youm, Y.-H., Ravussin, A., Galgani, J. E., Stadler, K., Mynatt, R. L., Ravussin, E., Stephens, J. M., & Dixit, V. D. (2011) · Nature Medicine · doi:10.1038/nm.2279 · Cited by 2,655 · see citing works
Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes
Kwon, H. S., & Koh, S.-H. (2020) · Translational Neurodegeneration · doi:10.1186/s40035-020-00221-2 · Cited by 2,595 · see citing works
Inflammation, metaflammation and immunometabolic disorders
Hotamisligil, G. S. (2017) · Nature · doi:10.1038/nature21363 · Cited by 2,570 · see citing works
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
What we talk about when we talk about fat
Rosen, E. D., & Spiegelman, B. M. (2014) · Cell · doi:10.1016/j.cell.2013.12.012 · Cited by 2,373 · see citing works
Nahrendorf, M., Swirski, F. K., Aikawa, E., Stangenberg, L., Wurdinger, T., Figueiredo, J.-L., Libby, P., Weissleder, R., & Pittet, M. J. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070885 · Cited by 2,300 · see citing works
Inflammatory links between obesity and metabolic disease
Lumeng, C. N., & Saltiel, A. R. (2011) · Journal of Clinical Investigation · doi:10.1172/jci57132 · Cited by 2,319 · see citing works
Self-citationNishimura, S., Manabe, I., Nagasaki, M., Eto, K., Yamashita, H., Ohsugi, M., Otsu, M., Hara, K., Ueki, K., Sugiura, S., et al. (2009) · Nature Medicine · doi:10.1038/nm.1964 · Cited by 2,230 · 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
Inflammatory mechanisms linking obesity and metabolic disease
Saltiel, A. R., & Olefsky, J. M. (2017) · Journal of Clinical Investigation · doi:10.1172/jci92035 · Cited by 2,212 · see citing works
Self-citationDifferential Roles of M1 and M2 Microglia in Neurodegenerative Diseases
Tang, Y., & Le, W. (2016) · Molecular Neurobiology · doi:10.1007/s12035-014-9070-5 · Cited by 2,190 · see citing works
Feuerer, M., Herrero, L., Cipolletta, D., Naaz, A., Wong, J., Nayer, A., Lee, J., Goldfine, A. B., Benoist, C., Shoelson, S., et al. (2009) · Nature Medicine · doi:10.1038/nm.2002 · Cited by 2,145 · see citing works
The metabolic signature of macrophage responses
Viola, A., Munari, F., Sánchez-Rodríguez, R., Scolaro, T., & Castegna, A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01462 · Cited by 2,021 · see citing works
Macrophage-specific PPARγ controls alternative activation and improves insulin resistance
Odegaard, J. I., Ricardo-Gonzalez, R. R., Goforth, M. H., Morel, C. R., Subramanian, V., Mukundan, L., Eagle, A. R., Vats, D., Brombacher, F., Ferrante, A. W., et al. (2007) · Nature · doi:10.1038/nature05894 · Cited by 2,107 · see citing works
Inflammation in obesity, diabetes, and related disorders
Rohm, T. V., Meier, D. T., Olefsky, J. M., & Donath, M. Y. (2022) · Immunity · doi:10.1016/j.immuni.2021.12.013 · Cited by 2,066 · 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
Arnold, L., Henry, A., Poron, F., Baba-Amer, Y., van Rooijen, N., Plonquet, A., Gherardi, R. K., & Chazaud, B. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070075 · Cited by 2,002 · see citing works
Adipose tissue inflammation and metabolic dysfunction in obesity
Kawai, T., Autieri, M. V., & Scalia, R. (2021) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00379.2020 · Cited by 1,947 · see citing works
NF-κB, Inflammation, and Metabolic Disease
Baker, R. G., Hayden, M. S., & Ghosh, S. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2010.12.008 · Cited by 1,952 · see citing works
Adipose tissue remodeling and obesity
Sun, K., Kusminski, C. M., & Scherer, P. E. (2011) · Journal of Clinical Investigation · doi:10.1172/jci45887 · Cited by 1,941 · see citing works
Jung, U. J., & Choi, M. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms15046184 · Cited by 1,898 · see citing works
Obesity, 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
Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future
Kahn, S. E., Cooper, M. E., & Del Prato, S. (2014) · The Lancet · doi:10.1016/s0140-6736(13)62154-6 · Cited by 1,743 · see citing works
Adipose tissue as an endocrine organ
Galić, S., Oakhill, J. S., & Steinberg, G. R. (2009) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.08.018 · Cited by 1,597 · see citing works
Chait, A., & den Hartigh, L. J. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00022 · Cited by 1,529 · 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
Adipose tissue dysfunction as determinant of obesity-associated metabolic complications
Longo, M., Zatterale, F., Naderi, J., Parrillo, L., Formisano, P., Raciti, G. A., Beguinot, F., & Miele, C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20092358 · Cited by 1,575 · see citing works
Adipose tissue dysfunction in obesity, diabetes, and vascular diseases
Hajer, G. R., van Haeften, T. W., & Visseren, F. L. J. (2008) · European Heart Journal · doi:10.1093/eurheartj/ehn387 · Cited by 1,410 · see citing works
The Role of Inflammation in Diabetes: Current Concepts and Future Perspectives
Tsalamandris, S., Antonopoulos, A. S., Oikonomou, E., Papamikroulis, G.-A., Vogiatzi, G., Papaioannou, S., Deftereos, S., & Tousoulis, D. (2019) · European Cardiology Review · doi:10.15420/ecr.2018.33.1 · Cited by 1,381 · see citing works
Eosinophils Sustain Adipose Alternatively Activated Macrophages Associated with Glucose Homeostasis
Wu, D., Molofsky, A. B., Liang, H.-E., Ricardo-González, R. R., Jouihan, H. A., Bando, J. K., Chawla, A., & Locksley, R. M. (2011) · Science · doi:10.1126/science.1201475 · Cited by 1,361 · see citing works
Normalization of obesity-associated insulin resistance through immunotherapy
Winer, S., Chan, Y., Paltser, G., Truong, D., Tsui, H., Bahrami, J., Dorfman, R., Wang, Y., Zielenski, J., Mastronardi, F., et al. (2009) · Nature Medicine · doi:10.1038/nm.2001 · Cited by 1,370 · see citing works
Genetics of gene expression and its effect on disease
Emilsson, V., Thorleifsson, G., Zhang, B., Leonardson, A. S., Zink, F., Zhu, J., Carlson, S., Helgason, A., Walters, G. B., Gunnarsdottir, S., et al. (2008) · Nature · doi:10.1038/nature06758 · Cited by 1,296 · see citing works
Macrophage Polarization in Bacterial Infections
Benoit, M. E., Desnues, B., & Mège, J. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.6.3733 · Cited by 1,317 · see citing works
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 · see citing works
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 · see citing works
Insulin sensitivity: Modulation by nutrients and inflammation
Schenk, S., Saberi, M., & Olefsky, J. M. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34260 · Cited by 1,191 · see citing works
Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis
Olsson, T., Barcellos, L., & Alfredsson, L. (2017) · Nature Reviews Neurology · doi:10.1038/nrneurol.2016.187 · Cited by 1,109 · see citing works
Chronic Adipose Tissue Inflammation Linking Obesity to Insulin Resistance and Type 2 Diabetes
Zatterale, F., Longo, M., Naderi, J., Raciti, G. A., Desiderio, A., Miele, C., & Beguinot, F. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2019.01607 · Cited by 1,180 · see citing works
Adipose tissue browning and metabolic health
Bartelt, A., & Heeren, J. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.204 · Cited by 1,177 · see citing works
Early Developmental Conditioning of Later Health and Disease: Physiology or Pathophysiology?
Hanson, M. A., & Gluckman, P. D. (2014) · Physiological Reviews · doi:10.1152/physrev.00029.2013 · Cited by 1,188 · see citing works
Inflammation and insulin resistance
de Luca, C., & Olefsky, J. M. (2008) · FEBS Letters · doi:10.1016/j.febslet.2007.11.057 · Cited by 1,161 · see citing works
M1 and M2 Macrophages: Oracles of Health and Disease
Mills, C. D. (2012) · Critical Reviews in Immunology · doi:10.1615/critrevimmunol.v32.i6.10 · Cited by 1,145 · see citing works
Overview of Epidemiology and Contribution of Obesity to Cardiovascular Disease
Bastien, M., Poirier, P., Lemieux, I., & Després, J.-P. (2014) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2013.10.016 · Cited by 1,125 · see citing works
Biology and therapeutic potential of interleukin-10
Saraiva, M., Vieira, P., & O’Garra, A. (2019) · The Journal of Experimental Medicine · doi:10.1084/jem.20190418 · Cited by 1,123 · 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
Inflammation and the pathogenesis of atrial fibrillation
Hu, Y., Chen, Y., Lin, Y., & Chen, S. (2015) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2015.2 · Cited by 1,101 · see citing works
Galli, S. J., Borregaard, N., & Wynn, T. A. (2011) · Nature Immunology · doi:10.1038/ni.2109 · Cited by 1,055 · see citing works
Winer, D. A., Winer, S., Shen, L., Wadia, P. P., Yantha, J., Paltser, G., Tsui, H., Wu, P., Davidson, M. G., Alonso, M. N., et al. (2011) · Nature Medicine · doi:10.1038/nm.2353 · Cited by 1,050 · see citing works
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 · see citing works
Adipose tissue and insulin resistance in obese
Ahmed, B., Sultana, R., & Greene, M. W. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111315 · Cited by 1,059 · see citing works
Adipose-tissue plasticity in health and disease
Sakers, A. P., Siqueira, M. K. D., Seale, P., & Villanueva, C. J. (2022) · Cell · doi:10.1016/j.cell.2021.12.016 · Cited by 1,061 · see citing works
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 · see citing works
Metabolic Inflammation and Insulin Resistance in Obesity
Wu, H., & Ballantyne, C. M. (2020) · Circulation Research · doi:10.1161/circresaha.119.315896 · Cited by 1,059 · see citing works
Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome
Maury, E., & Brichard, S. M. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.07.031 · Cited by 1,026 · see citing works
Adipocyte Death, Adipose Tissue Remodeling, and Obesity Complications
Strissel, K. J., Stancheva, Z., Miyoshi, H., Perfield, J. W., DeFuria, J., Jick, Z., Greenberg, A. S., & Obin, M. S. (2007) · Diabetes · doi:10.2337/db07-0767 · Cited by 1,007 · see citing works
Obesity, inflammation, and atherosclerosis
Rocha, V. Z., & Libby, P. (2009) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2009.55 · Cited by 994 · see citing works
Kauppinen, A., Suuronen, T., Ojala, J. O., Kaarniranta, K., & Salminen, A. (2013) · Cellular Signalling · doi:10.1016/j.cellsig.2013.06.007 · Cited by 1,001 · see citing works
Human epicardial adipose tissue: A review
Sacks, H. S., & Fain, J. N. (2007) · American Heart Journal · doi:10.1016/j.ahj.2007.03.019 · Cited by 971 · see citing works
Triggering and resolution of inflammation in NASH
Schuster, S., Cabrera, D., Arrese, M., & Feldstein, A. E. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0009-6 · Cited by 943 · see citing works
The Phagocytic Function of Macrophage-Enforcing Innate Immunity and Tissue Homeostasis
Hirayama, D., Iida, T., & Nakase, H. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms19010092 · Cited by 927 · see citing works
Metabolic Reprogramming of Macrophages
Freemerman, A. J., Johnson, A. R., Sacks, G. N., Milner, J. J., Kirk, E. L., Troester, M. A., Macintyre, A. N., Goraksha-Hicks, P., Rathmell, J. C., & Makowski, L. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.522037 · Cited by 956 · see citing works
Innate immunity in Alzheimer's disease
Heneka, M. T., Golenbock, D. T., & Latz, E. (2015) · Nature Immunology · doi:10.1038/ni.3102 · Cited by 902 · see citing works
Implications of macrophage polarization in autoimmunity
Funes, S. C., Rios, M., Escobar‐Vera, J., & Kalergis, A. M. (2018) · Immunology · doi:10.1111/imm.12910 · Cited by 1,005 · see citing works
Brown, B. N., Ratner, B. D., Goodman, S. B., Amar, S., & Badylak, S. F. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2012.02.034 · Cited by 926 · see citing works
Inflammation and Lipid Signaling in the Etiology of Insulin Resistance
Glass, C. K., & Olefsky, J. M. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.001 · Cited by 942 · see citing works
Obesity, Adipose Tissue and Vascular Dysfunction
Koenen, M., Hill, M. A., Cohen, P., & Sowers, J. R. (2021) · Circulation Research · doi:10.1161/circresaha.121.318093 · Cited by 953 · see citing works
Lumeng, C. N.-K., DelProposto, J. B., Westcott, D. J., & Saltiel, A. R. (2008) · Diabetes · doi:10.2337/db08-0872 · Cited by 919 · see citing works
Self-citationMolecular mechanisms of cancer development in obesity
Khandekar, M. J., Cohen, P., & Spiegelman, B. M. (2011) · Nature reviews. Cancer · doi:10.1038/nrc3174 · Cited by 906 · see citing works
Physiological and pathological cardiac hypertrophy
Shimizu, I., & Minamino, T. (2016) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2016.06.001 · Cited by 892 · see citing works
M2b macrophage polarization and its roles in diseases
Wang, L., Zhang, S.-X., Wu, H., Rong, X., & Guo, J. (2018) · Journal of Leukocyte Biology · doi:10.1002/jlb.3ru1018-378rr · Cited by 889 · see citing works
Roles for chemokines in liver disease
Marra, F., & Tacke, F. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.06.043 · Cited by 829 · see citing works
CD4 + CD25 + Foxp3 + regulatory T cells induce alternative activation of human monocytes/macrophages
Tiemessen, M. M., Jagger, A. L., Evans, H. G., van Herwijnen, M. J. C., John, S., & Taams, L. S. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706832104 · Cited by 856 · see citing works
Alternative M2 Activation of Kupffer Cells by PPARδ Ameliorates Obesity-Induced Insulin Resistance
Odegaard, J. I., Ricardo-González, R. R., Eagle, A. R., Vats, D., Morel, C. R., Goforth, M. H., Subramanian, V., Mukundan, L., Ferrante, A. W., & Chawla, A. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.04.003 · Cited by 840 · see citing works
Obesity, inflammation and the immune system
de Heredia, F. P., Gómez-Martínez, S., & Marcos, A. (2012) · Proceedings of the Nutrition Society · doi:10.1017/s0029665112000092 · Cited by 845 · see citing works
Tsukumo, D. M. L., Carvalho-Filho, M. A., Carvalheira, J. B. C., Prada, P. O., Hirabara, S. M., Schenka, A. A., Araújo, E. P., Vassallo, J., Curi, R., Velloso, L. A., et al. (2007) · Diabetes · doi:10.2337/db06-1595 · Cited by 826 · see citing works
RetractedKratz, 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 821 · see citing works
Ablation of CD11c-Positive Cells Normalizes Insulin Sensitivity in Obese Insulin Resistant Animals
Patsouris, D., Li, P.-P., Thapar, D., Chapman, J., Olefsky, J. M., & Neels, J. G. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.08.015 · Cited by 804 · see citing works
Imaging macrophages with nanoparticles
Weissleder, R., Nahrendorf, M., & Pittet, M. J. (2014) · Nature Materials · doi:10.1038/nmat3780 · Cited by 809 · see citing works
Cawthorn, W. P., & Sethi, J. K. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.11.051 · Cited by 792 · see citing works
High-Fat, Western-Style Diet, Systemic Inflammation, and Gut Microbiota: A Narrative Review
Malesza, I. J., Malesza, M., Walkowiak, J., Mussin, N. M., Walkowiak, D., Aringazina, R. A., Bartkowiak-Wieczorek, J., & Mądry, E. (2021) · Cells · doi:10.3390/cells10113164 · Cited by 807 · 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
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 780 · see citing works
Zhou, D., Huang, C., Lin, Z., Zhan, S., Kong, L., Fang, C., & Li, J. (2014) · Cellular Signalling · doi:10.1016/j.cellsig.2013.11.004 · Cited by 778 · see citing works
The multifaceted contributions of leukocyte subsets to atherosclerosis: lessons from mouse models
Weber, C., Zernecke, A., & Libby, P. (2008) · Nature reviews. Immunology · doi:10.1038/nri2415 · Cited by 777 · see citing works
Spiller, K. L., Nassiri, S., Witherel, C. E., Anfang, R. R., Ng, J., Nakazawa, K. R., Yu, T., & Vunjak-Novakovic, G. (2015) · Biomaterials · doi:10.1016/j.biomaterials.2014.10.017 · Cited by 773 · see citing works
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 · see citing works
Adipocytokines and the Metabolic Complications of Obesity
Rasouli, N., & Kern, P. A. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-1613 · Cited by 739 · see citing works
Adipokines: The missing link between insulin resistance and obesity
Antuna-Puente, B., Fève, B., Fellahi, S., & Bastard, J. (2008) · Diabetes & Metabolism · doi:10.1016/j.diabet.2007.09.004 · Cited by 738 · see citing works
Hypertension, diabetes, atherosclerosis and NASH: Cause or consequence?
Lonardo, A., Nascimbeni, F., Mantovani, A., & Targher, G. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2017.09.021 · Cited by 737 · see citing works
Protection from obesity and diabetes by blockade of TGF-β/smad3 signaling
Yadav, H., Quijano, C., Kamaraju, A. K., Gavrilova, O., Malek, R., Chen, W., Zerfas, P., Zhigang, D., Wright, E. C., Stuelten, C., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.04.013 · Cited by 709 · see citing works
Abderrazak, A., Syrovets, T., Couchie, D., Hadri, K. E., Friguet, B., Simmet, T., & Rouis, M. (2015) · Redox Biology · doi:10.1016/j.redox.2015.01.008 · Cited by 737 · see citing works
- Authors
- Lumeng, C. N., Bodzin, J. L., & Saltiel, A. R.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Saltiel, Alan R.
- Venue
- Journal of Clinical Investigation
- Published
- 2007-01-02
- Volume
- 117
- Issue
- 1
- Pages
- 175-184
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1716210
- OpenAlex
- W2145697808
- Cited by
- 4,664
- References
- 54
- Citations by year
- 2026: 157 · 2025: 214 · 2024: 227 · 2023: 224 · 2022: 256 · 2021: 324 · 2020: 320 · 2019: 304 · 2018: 290 · 2017: 322 · 2016: 296 · 2015: 290 · 2014: 286 · 2013: 319 · 2012: 226
- FWCI
- 92.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Michigan
- National Institutes of Health (HD028820)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK60591, R01DK060591)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007513, K12HD028820)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- obesity, adipose tissue macrophages, macrophage polarization, M1/M2 macrophages, insulin resistance, diet-induced obesity, CCR2, IL-10, TNF-α, adipocyte inflammation, high-fat diet, M2 macrophages
- MeSH terms
- Adipose Tissue, Animals, Base Sequence, Biological Transport, Energy Intake, Deoxyglucose, Dietary Fats, Disease Models, Animal, Macrophages, Male, Mice, Inbred C57BL, Mice, Obese, Obesity, 3T3 Cells, DNA Primers, Reverse Transcriptase Polymerase Chain Reaction, Mice
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
