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
Open accessAbstract
Obesity and type 2 diabetes are characterized by decreased insulin sensitivity, elevated concentrations of free fatty acids (FFAs), and increased macrophage infiltration in adipose tissue (AT). Here, we show that FFAs can cause activation of RAW264.7 cells primarily via the JNK signaling cascade and that TLR2 and TLR4 are upstream of JNK and help transduce FFA proinflammatory signals. We also demonstrate that F4/80(+)CD11b(+)CD11c(+) bone marrow-derived dendritic cells (BMDCs) have heightened proinflammatory activity compared with F4/80(+)CD11b(+)CD11c(-) bone marrow-derived macrophages and that the proinflammatory activity and JNK phosphorylation of BMDCs, but not bone marrow-derived macrophages, was further increased by FFA treatment. F4/80(+)CD11b(+)CD11c(+) cells were found in AT, and the proportion and number of these cells in AT is increased in ob/ob mice and by feeding wild type mice a high fat diet for 1 and 12 weeks. AT F4/80(+)CD11b(+)CD11c(+) cells express increased inflammatory markers compared with F4/80(+)CD11b(+)CD11c(-) cells, and FFA treatment increased inflammatory responses in these cells. In addition, we found that CD11c expression is increased in skeletal muscle of high fat diet-fed mice and that conditioned medium from FFA-treated wild type BMDCs, but not TLR2/4 DKO BMDCs, can induce insulin resistance in L6 myotubes. Together our results show that FFAs can activate CD11c(+) myeloid proinflammatory cells via TLR2/4 and JNK signaling pathways, thereby promoting inflammation and subsequent cellular insulin resistance.
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Free fatty acid products from necrotic adipocytes cause pro-inflammatory activation of macrophages through TLR-2 and TLR-4 signaling.
“A number of free fatty acid products released from necrotic adipocytes have been shown to cause pro-inflammatory activation of macrophages through TLR-2 and TLR-4 signaling pathways, suggesting a potential mechanism by which obesity-induced inflammation may occur [73,74].”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [73]
M2 macrophages are positive for F4/80 and CD11b but negative for CD11c.
“Similar to M1 macrophages, they are positive for F4/80 and CD11b, but they are negative for CD11c (105).”
From Insulin sensitivity: Modulation by nutrients and inflammation (2008) · cites this paper as [105]
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 [105]
In obesity, most of the expanded adipose tissue macrophage population consists of proinflammatory macrophages positive for F4/80, CD11b, and CD11c.
“In obesity, the major component of the increased ATM content is composed of proinflammatory macrophages that are triply positive for the surface markers F4/80, CD11b, and CD11c (92,105).”
From Insulin sensitivity: Modulation by nutrients and inflammation (2008) · cites this paper as [105]
Macrophages and adipocytes lacking Tlr2, Tlr4, or both do not activate inflammation.
“Activation of inflammation is prevented in macrophages and adipocytes that are deficient in Tlr2, Tlr4, or Tlr2/Tlr4 (105, 114-116).”
From Insulin sensitivity: Modulation by nutrients and inflammation (2008) · cites this paper as [105]
Adipose tissue macrophages sit in a lipid-rich environment, and fatty acids can broadly activate their inflammatory program.
“Clearly, ATMs exist in a lipid-rich environment and fatty acids can broadly activate the macrophage inflammatory program (105, 114-116).”
From Insulin sensitivity: Modulation by nutrients and inflammation (2008) · cites this paper as [105]
Tlr2/Tlr4 expression is elevated in macrophages positive for F4/80, CD11b, and CD11c.
“Interestingly, the expression of Tlr2/Tlr4 is increased in macrophages that are triply positive for F4/80, CD11b, and CD11c (105)”
From Insulin sensitivity: Modulation by nutrients and inflammation (2008) · cites this paper as [105]
TLR2 and TLR4 pattern recognition receptors are important in fatty-acid-induced macrophage activation.
“An important component of these fatty acid-induced activation events are the pattern recognition receptors TLR2 and TLR4 (105, 114-116).”
From Insulin sensitivity: Modulation by nutrients and inflammation (2008) · cites this paper as [105]
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1 retracted
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
RetractedObesity 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
Defective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in <i>Tlr4</i> Gene
Poltorak, A., He, X., Smirnova, I., Liu, M.-Y., Huffel, C. V., Du, X., Birdwell, D., Alejos, E., Silva, M., Galanos, C., et al. (1998) · Science · doi:10.1126/science.282.5396.2085 · Cited by 7,631 · 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
Obesity induces a phenotypic switch in adipose tissue macrophage polarization
Lumeng, C. N., Bodzin, J. L., & Saltiel, A. R. (2007) · Journal of Clinical Investigation · doi:10.1172/jci29881 · Cited by 4,664 · see citing works
Inflammation, stress, and diabetes
Wellen, K. E., & Hotamisligil, G. S. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25102 · Cited by 4,143 · see citing works
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 · see citing works
Hoshino, K., Takeuchi, O., Kawai, T., Sanjo, H., Ogawa, T., Takeda, Y., Takeda, K., & Akira, S. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.7.3749 · Cited by 3,374 · 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
A central role for JNK in obesity and insulin resistance
Hirosumi, J., Tuncman, G., Chang, L., Görgün, C. Z., Uysal, K. T., Maeda, K., Karin, M., & Hotamisligil, G. S. (2002) · Nature · doi:10.1038/nature01137 · Cited by 3,359 · see citing works
Toll-like receptors in innate immunity
Takeda, K. (2004) · International Immunology · doi:10.1093/intimm/dxh186 · Cited by 3,328 · see citing works
LPS induction of gene expression in human monocytes.
Guha, M., & Mackman, N. (2001) · Cellular Signalling · doi:10.1016/s0898-6568(00)00149-2 · Cited by 2,441 · see citing works
Inflammation: the link between insulin resistance, obesity and diabetes
Dandona, P. (2004) · Trends in Immunology · doi:10.1016/j.it.2003.10.013 · Cited by 2,170 · see citing works
Yuan, M., Konstantopoulos, N., Lee, J., Hansen, L., Li, Z.-W., Karin, M., & Shoelson, S. E. (2001) · Science · doi:10.1126/science.1061620 · Cited by 1,884 · 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
Self-citationRole of Fatty Acids in the Pathogenesis of Insulin Resistance and NIDDM
Boden, G. (1997) · Diabetes · doi:10.2337/diab.46.1.3 · Cited by 1,728 · see citing works
Negative regulation of Toll-like receptor-mediated immune responses
Liew, F. Y., Xu, D., Brint, E. K., & O'Neill, L. A. J. (2005) · Nature Reviews Immunology · doi:10.1038/nri1630 · Cited by 1,509 · see citing works
Macrophage Polarization Comes of Age
Mantovani, Sica, & Locati, M. (2005) · Immunity · doi:10.1016/j.immuni.2005.10.001 · Cited by 1,259 · 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
Emerging roles of PPARS in inflammation and immunity
Daynes, R. A., & Jones, D. C. (2002) · Nature reviews. Immunology · doi:10.1038/nri912 · Cited by 922 · see citing works
Peroxisome proliferator-activated receptors in inflammation control
Delerive, P., Fruchart, J., & Staels, B. (2001) · Journal of Endocrinology · doi:10.1677/joe.0.1690453 · Cited by 755 · see citing works
Curat, C. A., Wegner, V., Sengenès, C., Miranville, A., Tonus, C., Busse, R., & Bouloumié, A. (2006) · Diabetologia · doi:10.1007/s00125-006-0173-z · Cited by 693 · see citing works
Tripathy, D., Mohanty, P., Dhindsa, S., Syed, T., Ghanim, H., Aljada, A., & Dandona, P. (2003) · Diabetes · doi:10.2337/diabetes.52.12.2882 · Cited by 658 · see citing works
Circulating 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
Lee, J. Y., Zhao, L., Youn, H. S., Weatherill, A. R., Tapping, R. I., Feng, L., Lee, W. H., Fitzgerald, K. A., & Hwang, D. H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312990200 · Cited by 493 · see citing works
Binding of long-chain fatty acids to bovine serum albumin
Spector, A. A., John, K. M., & Fletcher, J. (1969) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)42649-5 · Cited by 485 · see citing works
Nguyen, M. T. A., Satoh, H., Favelyukis, S., Babendure, J. L., Imamura, T., Sbodio, J. I., Zalevsky, J., Dahiyat, B. I., Chi, N.-W., & Olefsky, J. M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m504611200 · Cited by 411 · see citing works
Self-citationAn immune origin of type 2 diabetes?
Kolb, H., & Mandrup-Poulsen, T. (2005) · Diabetologia · doi:10.1007/s00125-005-1764-9 · Cited by 394 · see citing works
Evidence for a Potent Antiinflammatory Effect of Rosiglitazone
Mohanty, P., Aljada, A., Ghanim, H., Hofmeyer, D., Tripathy, D., Syed, T., Al-Haddad, W., Dhindsa, S., & Dandona, P. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-032103 · Cited by 375 · see citing works
Role of macrophage tissue infiltration in metabolic diseases
Bouloumié, A., Curat, C. A., Sengenès, C., Lolmède, K., Miranville, A., & Busse, R. (2005) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/01.mco.0000172571.41149.52 · Cited by 262 · see citing works
Interaction between free fatty acids and glucose metabolism
Boden, G. H. (2002) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/00075197-200209000-00014 · Cited by 222 · see citing works
ICAM-1 expression in adipose tissue: effects of diet-induced obesity in mice
Brake, D. K., Smith, E. O., Mersmann, H. J., Smith, C. W., & Robker, R. L. (2006) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00008.2006 · Cited by 150 · see citing works
Kraegen, E. W., Cooney, G. J., Ye, J.-M., Thompson, A., & Furler, S. M. (2001) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-2001-18581 · Cited by 130 · see citing works
Bone marrow–specific Cap gene deletion protects against high-fat diet–induced insulin resistance
Lesniewski, L. A., Hosch, S. E., Neels, J. G., de Luca, C., Pashmforoush, M., Lumeng, C. N.-K., Chiang, S.-H., Scadeng, M., Saltiel, A. R., & Olefsky, J. M. (2007) · Nature Medicine · doi:10.1038/nm1550 · Cited by 114 · see citing works
Self-citationMouse Cell Surface Antigens: Nomenclature and Immunophenotyping
Lai, L., Alaverdi, N., Maltais, L. J., & Morse, H. C. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.160.8.3861 · Cited by 105 · 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
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Sorted by citations
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
Self-citationHuman nutrition, the gut microbiome and the immune system
Kau, A. L., Ahern, P. P., Griffin, N. W., Goodman, A. L., & Gordon, J. I. (2011) · Nature · doi:10.1038/nature10213 · Cited by 2,588 · 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
Oh, D. Y., Talukdar, S., Bae, E. J., Imamura, T., Morinaga, H., Fan, W., Li, P., Lu, W. J., Watkins, S. M., & Olefsky, J. M. (2010) · Cell · doi:10.1016/j.cell.2010.07.041 · Cited by 2,428 · see citing works
Self-citationInflammation 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
Self-citationInflammation 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
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 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
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
Fatty acid–induced NLRP3-ASC inflammasome activation interferes with insulin signaling
Wen, H., Gris, D., Lei, Y. L., Jha, S., Zhang, L., Huang, M. T.-H., Brickey, W. J., & Ting, J. P. ‐. (2011) · Nature Immunology · doi:10.1038/ni.2022 · Cited by 1,811 · see citing works
Sun, D., Zhuang, X., Xiang, X., Liu, Y., Zhang, S., Liu, C., Barnes, S., Grizzle, W. E., Miller, D., & Zhang, H. (2010) · Molecular Therapy · doi:10.1038/mt.2010.105 · Cited by 1,579 · 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
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
Self-citationAdapting to obesity with adipose tissue inflammation
Reilly, S. M., & Saltiel, A. R. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.90 · Cited by 1,204 · 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
Self-citationYing, W., Riopel, M., Bandyopadhyay, G., Dong, Y., Birmingham, A., Seo, J. B., Ofrecio, J. M., Wollam, J., Hernandez-Carretero, A., Fu, W., et al. (2017) · Cell · doi:10.1016/j.cell.2017.08.035 · Cited by 1,191 · see citing works
Self-citationMetabolic 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
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
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
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
Self-citationThe 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
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
“pathways, suggesting a potential mechanism by which obesityinduced inflammation may occur [73,74].”
BackgroundFetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance
Pal, D., Dasgupta, S., Kundu, R., Maitra, S., Das, G., Mukhopadhyay, S., Ray, S., Majumdar, S. S., & Bhattacharya, S. (2012) · Nature Medicine · doi:10.1038/nm.2851 · Cited by 922 · see citing works
Amar, J., Chabo, C., Waget, A., Klopp, P., Vachoux, C., Bermúdez‐Humarán, L. G., Smirnova, N. F., Bergé, M., Sulpice, T., Lahtinen, S. J., et al. (2011) · EMBO Molecular Medicine · doi:10.1002/emmm.201100159 · Cited by 835 · 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
Self-citationMacrophages, Immunity, and Metabolic Disease
McNelis, J., & Olefsky, J. M. (2014) · Immunity · doi:10.1016/j.immuni.2014.05.010 · Cited by 728 · see citing works
Self-citationWeight loss and lipolysis promote a dynamic immune response in murine adipose tissue
Kosteli, A., Sugaru, E., Haemmerle, G., Martin, J. F., Lei, J., Zechner, R., & Ferrante, A. W. (2010) · Journal of Clinical Investigation · doi:10.1172/jci42845 · Cited by 726 · see citing works
Impact of Obesity and Metabolic Syndrome on Immunity
Andersen, C. J., Murphy, K. E., & Fernandez, M. L. (2016) · Advances in Nutrition · doi:10.3945/an.115.010207 · Cited by 701 · see citing works
Skeletal muscle inflammation and insulin resistance in obesity
Wu, H., & Ballantyne, C. M. (2017) · Journal of Clinical Investigation · doi:10.1172/jci88880 · Cited by 695 · see citing works
Targeting inflammation in the treatment of type 2 diabetes: time to start
Donath, M. Y. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4275 · Cited by 690 · see citing works
The Origins and Drivers of Insulin Resistance
Johnson, A. M. F., & Olefsky, J. M. (2013) · Cell · doi:10.1016/j.cell.2013.01.041 · Cited by 639 · see citing works
Self-citationAlternative macrophage activation and metabolism
Odegaard, J. I., & Chawla, A. (2011) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-011110-130138 · Cited by 640 · see citing works
Nuclear receptor transrepression pathways that regulate inflammation in macrophages and T cells
Glass, C. K., & Saijo, K. (2010) · Nature Reviews Immunology · doi:10.1038/nri2748 · Cited by 619 · see citing works
Self-citationWentworth, J. M., Naselli, G., Brown, W. A., Doyle, L., Phipson, B., Smyth, G. K., Wabitsch, M., O’Brien, P. E., & Harrison, L. C. (2010) · Diabetes · doi:10.2337/db09-0287 · Cited by 609 · see citing works
Properties and functions of adipose tissue macrophages in obesity
Russo, L., & Lumeng, C. N.-K. (2018) · Immunology · doi:10.1111/imm.13002 · Cited by 601 · see citing works
Wan, Y., Wang, F., Yuan, J., Li, J., Jiang, D., Zhang, J., Li, H., Wang, R., Tang, J., Huang, T., et al. (2019) · Gut · doi:10.1136/gutjnl-2018-317609 · Cited by 598 · see citing works
Saturated fatty acids activate TLR-mediated proinflammatory signaling pathways
Huang, S., Rutkowsky, J. M., Snodgrass, R. G., Ono‐Moore, K. D., Schneider, D. A., Newman, J. W. I., Adams, S. H., & Hwang, D. H. (2012) · Journal of Lipid Research · doi:10.1194/jlr.d029546 · Cited by 593 · see citing works
Orchestration of Metabolism by Macrophages
Biswas, S. K., & Mantovani, A. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2011.11.013 · Cited by 586 · see citing works
Inflammation Is Necessary for Long-Term but Not Short-Term High-Fat Diet–Induced Insulin Resistance
Lee, Y. S., Li, P., Huh, J. Y., Hwang, I. J., Lu, M., Kim, J. I., Ham, M., Talukdar, S., Chen, A., Lu, W. J., et al. (2011) · Diabetes · doi:10.2337/db11-0194 · Cited by 566 · see citing works
Self-citationWong, S. W., Kwon, M.-J., Choi, A. M. K., Kim, H.-P., Nakahira, K., & Hwang, D. H. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.044065 · Cited by 562 · see citing works
Kennedy, A. J., Martinez, K., Chuang, C., LaPoint, K., & McIntosh, M. (2008) · Journal of Nutrition · doi:10.3945/jn.108.098269 · Cited by 562 · see citing works
The Role of Adipose Tissue and Adipokines in Obesity-Related Inflammatory Diseases
Balistreri, C. R., Caruso, C., & Candore, G. (2010) · Mediators of Inflammation · doi:10.1155/2010/802078 · Cited by 554 · see citing works
The role of adipose tissue immune cells in obesity and low-grade inflammation
Mraz, M., & Haluzik, M. (2014) · Journal of Endocrinology · doi:10.1530/joe-14-0283 · Cited by 543 · see citing works
The obese adipose tissue microenvironment in cancer development and progression
Quail, D. F., & Dannenberg, A. J. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0126-x · Cited by 542 · see citing works
Panduro, M., Benoist, C., & Mathis, D. (2016) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032712-095948 · Cited by 536 · see citing works
McArdle, M. A., Finucane, O. M., Connaughton, R. M., McMorrow, A. M., & Roche, H. M. (2013) · Frontiers in Endocrinology · doi:10.3389/fendo.2013.00052 · Cited by 532 · see citing works
Endogenous ligands of TLR2 and TLR4: agonists or assistants?
Erridge, C. (2010) · Journal of Leukocyte Biology · doi:10.1189/jlb.1209775 · Cited by 518 · see citing works
Maternal obesity and fetal metabolic programming: a fertile epigenetic soil
Heerwagen, M. J. R., Miller, M. R., Barbour, L. A., & Friedman, J. E. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00310.2010 · Cited by 520 · see citing works
Korbecki, J., & Bajdak-Rusinek, K. (2019) · Inflammation Research · doi:10.1007/s00011-019-01273-5 · Cited by 517 · see citing works
Adipose Tissue Macrophages Promote Myelopoiesis and Monocytosis in Obesity
Nagareddy, P. R., Kraakman, M. J., Masters, S. L., Stirzaker, R. A., Gorman, D. J., Grant, R. W., Dragoljevic, D., Hong, E. S., Abdel‐Latif, A., Smyth, S. S., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.03.029 · Cited by 510 · see citing works
Type 2 diabetes mellitus: From a metabolic disorder to an inflammatory condition
Hameed, I., Masoodi, S. R., Mir, S. A., Nabi, M., Ghazanfar, K., & Ganai, B. A. (2015) · World Journal of Diabetes · doi:10.4239/wjd.v6.i4.598 · Cited by 513 · see citing works
Immune Regulation of Metabolic Homeostasis in Health and Disease
Brestoff, J. R., & Artis, D. (2015) · Cell · doi:10.1016/j.cell.2015.02.022 · Cited by 498 · see citing works
Insulin Resistance, Obesity and Lipotoxicity
Yazıcı, D., & Sezer, H. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-48382-5_12 · Cited by 507 · see citing works
Insulin resistance causes inflammation in adipose tissue
Shimobayashi, M., Albert, V., Woelnerhanssen, B., Frei, I. C., Weissenberger, D., Meyer-Gerspach, A. C., Clement, N., Moes, S., Colombi, M., Meier, J. A., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci96139 · Cited by 480 · see citing works
Seimon, T. A., Nadolski, M. J., Liao, X., Magallon, J., Nguyen, M. T., Feric, N. T., Koschinsky, M. L., Harkewicz, R., Witztum, J. L., Tsimikas, S., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.09.010 · Cited by 478 · see citing works
Self-citationLancaster, G. I., Langley, K. G., Berglund, N. A., Kammoun, H. L., Reibe, S., Estévez, E., Weir, J. M., Mellett, N. A., Pernes, G., Conway, J. R. W., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.03.014 · Cited by 465 · see citing works
Resolvins, Specialized Proresolving Lipid Mediators, and Their Potential Roles in Metabolic Diseases
Spite, M., Clària, J., & Serhan, C. N. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2013.10.006 · Cited by 464 · see citing works
Obesity and asthma: Possible mechanisms
Shore, S. A. (2008) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2008.03.004 · Cited by 454 · see citing works
Saberi, M., Woods, N.-B., de Luca, C., Schenk, S., Lu, J. C., Bandyopadhyay, G., Verma, I. M., & Olefsky, J. M. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.09.006 · Cited by 456 · see citing works
“In fact, JNK1 is an obligatory component for the ability of fatty acids and Tlr4 to activate inflammatory pathways and to increase TNF-a secretion (Nguyen et al., 2007).”
BackgroundInfluentialSelf-citationAdipose tissue as an immunological organ
Grant, R. W., & Dixit, V. D. (2015) · Obesity · doi:10.1002/oby.21003 · Cited by 453 · see citing works
The role of infiltrating immune cells in dysfunctional adipose tissue
Guzik, T. J., Skiba, D. S., Touyz, R. M., & Harrison, D. G. (2017) · Cardiovascular Research · doi:10.1093/cvr/cvx108 · Cited by 453 · see citing works
Tumor-associated macrophages: unwitting accomplices in breast cancer malignancy
Williams, C. B., Yeh, E. S., & Soloff, A. (2016) · npj Breast Cancer · doi:10.1038/npjbcancer.2015.25 · Cited by 438 · see citing works
Arachidonic Acid Metabolites in Cardiovascular and Metabolic Diseases
Sonnweber, T., Pizzini, A., Nairz, M., Weiß, G., & Tancevski, I. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113285 · Cited by 439 · see citing works
An Integrated View of Immunometabolism
Lee, Y. S., Wollam, J., & Olefsky, J. M. (2018) · Cell · doi:10.1016/j.cell.2017.12.025 · Cited by 440 · see citing works
Self-citationThe impact of obesity on the immune response to infection
Milner, J. J., & Beck, M. A. (2012) · Proceedings of The Nutrition Society · doi:10.1017/s0029665112000158 · Cited by 439 · see citing works
Immunological Goings-on in Visceral Adipose Tissue
Mathis, D. J. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.05.008 · Cited by 433 · see citing works
Gauffin-Cano, P., Santacruz, A., Moya-Pérez, Á., & Sanz, Y. (2012) · PLoS ONE · doi:10.1371/journal.pone.0041079 · Cited by 438 · see citing works
Tanti, J.-F., & Jager, J. (2009) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2009.07.004 · Cited by 430 · see citing works
Adipose tissue macrophages: going off track during obesity
Boutens, L., & Stienstra, R. (2016) · Diabetologia · doi:10.1007/s00125-016-3904-9 · Cited by 430 · see citing works
SIRT1 inhibits inflammatory pathways in macrophages and modulates insulin sensitivity
Yoshizaki, T., Schenk, S., Imamura, T., Babendure, J. L., Sonoda, N., Bae, E. J., Oh, D. Y., Lu, M. M., Milne, J. C., Westphal, C. H., et al. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00417.2009 · Cited by 420 · see citing works
Self-citationRogers, N. H., Perfield, J. W., Strissel, K. J., Obin, M. S., & Greenberg, A. S. (2009) · Endocrinology · doi:10.1210/en.2008-1405 · Cited by 419 · see citing works
Obesity, Inflammation, and Cardiovascular Risk
Mathieu, P., Lemieux, I., & Després, J. (2010) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2009.311 · Cited by 416 · see citing works
Bertola, A., Ciucci, T., Rousseau, D., Bourlier, V., Duffaut, C., Bonnafous, S., Blin‐Wakkach, C., Anty, R., Iannelli, A., Gugenheim, J., et al. (2012) · Diabetes · doi:10.2337/db11-1274 · Cited by 403 · see citing works
Macrophage polarization and plasticity in health and disease
Biswas, S. K., Chittezhath, M., Shalova, I. N., & Lim, J.-Y. (2012) · Immunologic Research · doi:10.1007/s12026-012-8291-9 · Cited by 396 · see citing works
Elevated Toll-Like Receptor 4 Expression and Signaling in Muscle From Insulin-Resistant Subjects
Reyna, S. M., Ghosh, S., Tantiwong, P., Meka, C. S. R., Eagan, P. A., Jenkinson, C. P., Cersósimo, E., DeFronzo, R. A., Coletta, D. K., Sriwijitkamol, A., et al. (2008) · Diabetes · doi:10.2337/db08-0038 · Cited by 381 · see citing works
Fast food fever: reviewing the impacts of the Western diet on immunity
Myles, I. A. (2014) · Nutrition Journal · doi:10.1186/1475-2891-13-61 · Cited by 390 · see citing works
Contribution of Adipose Tissue Inflammation to the Development of Type 2 Diabetes Mellitus
Burhans, M. S., Hagman, D. K., Kuzma, J. N., Schmidt, K. A., & Kratz, M. (2018) · Comprehensive physiology · doi:10.1002/cphy.c170040 · Cited by 427 · see citing works
Macrophage polarization and meta-inflammation
Li, C., Xu, M. M., Wang, K., Adler, A. J., Vella, A. T., & Zhou, B. (2017) · Translational research · doi:10.1016/j.trsl.2017.10.004 · Cited by 369 · see citing works
Shaul, M. E., Bennett, G., Strissel, K. J., Greenberg, A. S., & Obin, M. S. (2010) · Diabetes · doi:10.2337/db09-1402 · Cited by 370 · see citing works
Increased Macrophage Migration Into Adipose Tissue in Obese Mice
Oh, D. Y., Morinaga, H., Talukdar, S., Bae, E. J., & Olefsky, J. M. (2011) · Diabetes · doi:10.2337/db11-0860 · Cited by 365 · see citing works
Self-citationObesity Is Associated with Inflammation and Elevated Aromatase Expression in the Mouse Mammary Gland
Subbaramaiah, K., Howe, L. R., Bhardwaj, P., Du, B., Gravaghi, C., Yantiss, R. K., Zhou, X. K., Blaho, V. A., Hla, T., Yang, P., et al. (2011) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-10-0381 · Cited by 362 · see citing works
RetractedThijssen, E., van Caam, A., & van der Kraan, P. M. (2014) · Lara D. Veeken · doi:10.1093/rheumatology/keu464 · Cited by 360 · see citing works
Mechanisms Linking Obesity, Chronic Kidney Disease, and Fatty Liver Disease
Ix, J. H., & Sharma, K. (2010) · Journal of the American Society of Nephrology · doi:10.1681/asn.2009080820 · Cited by 351 · see citing works
JNK1 and IKKβ: molecular links between obesity and metabolic dysfunction
Solinas, G., & Karin, M. (2010) · The FASEB Journal · doi:10.1096/fj.09-151340 · Cited by 347 · see citing works
Molecular Signatures of Obstructive Sleep Apnea in Adults: A Review and Perspective
Arnardóttir, E. S., Mackiewicz, M., Gíslason, Þ., Teff, K. L., & Pack, A. I. (2009) · SLEEP · doi:10.1093/sleep/32.4.447 · Cited by 347 · see citing works
Leptin and the maintenance of elevated body weight
Pan, W. W., & Myers, M. G. (2018) · Nature reviews. Neuroscience · doi:10.1038/nrn.2017.168 · Cited by 344 · see citing works
Galić, S., Fullerton, M. D., Schertzer, J. D., Sikkema, S. R., Marcinko, K., Walkley, C. R., Izon, D. J., Honeyman, J. E., Chen, Z., van Denderen, B. J., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci58577 · Cited by 344 · see citing works
Inflammation in obesity and diabetes: islet dysfunction and therapeutic opportunity
Donath, M. Y., Dalmas, É., Sauter, N. S., & Böni-Schnetzler, M. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.05.001 · Cited by 338 · see citing works
Böni‐Schnetzler, M., Boller, S., Debray, S., Bouzakri, K., Meier, D. T., Prazak, R., Kerr-Conte, J. A., Pattou, F. N., Ehses, J. A., Schuit, F. C., et al. (2009) · Endocrinology · doi:10.1210/en.2009-0543 · Cited by 344 · see citing works
Toll-like receptors: linking inflammation to metabolism
Könner, A. C., & Brüning, J. C. (2010) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2010.08.007 · Cited by 327 · see citing works
Role of Leptin in Inflammation and Vice Versa
Pérez-Pérez, A., Sánchez-Jiménez, F., Vilariño-García, T., & Sánchez-Margalet, V. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21165887 · Cited by 330 · see citing works
Islet Inflammation Impairs the Pancreatic β-Cell in Type 2 Diabetes
Donath, M. Y., Böni‐Schnetzler, M., Ellingsgaard, H., & Ehses, J. A. (2009) · Physiology · doi:10.1152/physiol.00032.2009 · Cited by 327 · see citing works
Joosten, L. A. B., Netea, M. G., Mylona, E. E., Koenders, M. I., Malireddi, R. K. S., Oosting, M., Stienstra, R., van de Veerdonk, F. L., Stalenhoef, A. F. H., Giamarellos‐Bourboulis, E. J., et al. (2010) · Arthritis & Rheumatism · doi:10.1002/art.27667 · Cited by 330 · see citing works
Inflammation and metabolic cardiomyopathy
Nishida, K., & Otsu, K. (2017) · Cardiovascular Research · doi:10.1093/cvr/cvx012 · Cited by 329 · see citing works
Nani, A., Murtaza, B., Sayed Khan, A., Khan, N. A., & Hichami, A. (2021) · Molecules · doi:10.3390/molecules26040985 · Cited by 321 · see citing works
Lee, Y.-S., Park, M.-S., Choung, J.-S., Kim, S.-S., Oh, H.-H., Choi, C.-S., Ha, S.-Y., Kang, Y., Kim, Y., & Jun, H.-S. (2012) · Diabetologia · doi:10.1007/s00125-012-2592-3 · Cited by 319 · see citing works
Modulation of gut microbiota by antibiotics improves insulin signalling in high-fat fed mice
Carvalho, B. M., Guadagnini, D., Tsukumo, D. M. L., Schenka, A. A., Latuf-Filho, P., Vassallo, J., Dias, J. C., Kubota, L. T., Carvalheira, J. B. C., & Saad, M. J. A. (2012) · Diabetologia · doi:10.1007/s00125-012-2648-4 · Cited by 314 · see citing works
Chemotherapy-enhanced inflammation may lead to the failure of therapy and metastasis
Vyas, D., Laput, G. P., & Vyas, A. K. (2014) · OncoTargets and Therapy · doi:10.2147/ott.s60114 · Cited by 310 · see citing works
Ribas, V., Nguyen, M. T. A., Henstridge, D. C., Nguyen, A.-K., Beaven, S. W., Watt, M. J., & Hevener, A. L. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00504.2009 · Cited by 309 · see citing works
Self-citation
- Authors
- 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.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Nguyen, M. T. Audrey
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2007-11
- Volume
- 282
- Issue
- 48
- Pages
- 35279-35292
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2063131576
- Cited by
- 1,035
- References
- 36
- Citations by year
- 2026: 26 · 2025: 37 · 2024: 29 · 2023: 32 · 2022: 52 · 2021: 52 · 2020: 45 · 2019: 55 · 2018: 48 · 2017: 66 · 2016: 67 · 2015: 59 · 2014: 84 · 2013: 91 · 2012: 74
- FWCI
- 31.77
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- National Institutes of Health (5r03ar049416-03, DK 074868)
- University of California, San Diego
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 074868, DK-33651, P01DK074868)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR049416)
- 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
- free fatty acids, adipose tissue macrophages, TLR2, TLR4, JNK signaling, dendritic cells, CD11c, bone marrow-derived macrophages, adipose tissue inflammation, insulin resistance, obesity, type 2 diabetes, high-fat diet, ob/ob mice, skeletal muscle inflammation, myotubes
- MeSH terms
- Adipose Tissue, Animals, Bone Marrow Cells, Fatty Acids, Nonesterified, Inflammation, Insulin Resistance, Macrophages, Male, Mice, Inbred C57BL, Models, Biological, Signal Transduction, CD11b Antigen, CD11c Antigen, MAP Kinase Kinase 4, Toll-Like Receptor 2, Toll-Like Receptor 4, Mice
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