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Cited by 1,059Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismCardiovascular Disease and Adiposity

Metabolic Inflammation and Insulin Resistance in Obesity

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Wu, Huaizhu, Ballantyne, Christie M.·2020·Circulation Research
DOI 10.1161/circresaha.119.315896PMC PMC7250139
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Abstract

Obesity is becoming an epidemic in the United States and worldwide and increases risk for many diseases, particularly insulin resistance, type 2 diabetes mellitus, and cardiovascular disease. The mechanisms linking obesity with these diseases remain incompletely understood. Over the past 2 to 3 decades, it has been recognized that in obesity, inflammation, with increased accumulation and inflammatory polarization of immune cells, takes place in various tissues, including adipose tissue, skeletal muscle, liver, gut, pancreatic islet, and brain and may contribute to obesity-linked metabolic dysfunctions, leading to insulin resistance and type 2 diabetes mellitus. Therapies targeting inflammation have shed light on certain obesity-linked diseases, including type 2 diabetes mellitus and atherosclerotic cardiovascular disease, but remain to be tested further and confirmed in clinical trials. This review focuses on inflammation in adipose tissue and its potential role in insulin resistance associated with obesity.

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  1. McNelis JC, Olefsky JM. Macrophages, immunity, and metabolic disease. Immunity. 2014;41:36-48. doi: 10.1016/j.immuni.2014.05.010 · DOI
  2. Hotamisligil GS. Inflammation, metaflammation and immunometabolic disor- ders. Nature. 2017;542:177-185. doi: 10.1038/nature21363 · DOI · Paper page
  3. Lackey DE, Olefsky JM. Regulation of metabolism by the innate immune sys- tem. Nat Rev Endocrinol. 2016;12:15-28. doi: 10.1038/nrendo.2015.189 · DOI · Paper page
  4. McLaughlin T, Ackerman SE, Shen L, Engleman E. Role of innate and adaptive immunity in obesity-associated metabolic disease. J Clin Invest. 2017;127:5-13. doi: 10.1172/JCI88876 · DOI
  5. Fahy JV. Type 2 inflammation in asthma-present in most, absent in many. Nat Rev Immunol. 2015;15:57-65. doi: 10.1038/nri3786 · DOI
  6. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Sci- ence. 1993;259:87-91. doi: 10.1126/science.7678183 · DOI · Paper page
  7. Wu H, Ghosh S, Perrard XD, Feng L, Garcia GE, Perrard JL, Sweeney JF, Peterson LE, Chan L, Smith CW, et al. T-cell accumulation and regu- lated on activation, normal T cell expressed and secreted upregula- tion in adipose tissue in obesity. Circulation. 2007;115:1029-1038. doi: 10.1161/CIRCULATIONAHA.106.638379 · DOI
  8. Jiao P, Chen Q, Shah S, Du J, Tao B, Tzameli I, Yan W, Xu H. Obesity-related upregulation of monocyte chemotactic factors in adipocytes: involvement of nuclear factor-kappaB and c-Jun NH2-terminal kinase pathways. Diabetes. 2009;58:104-115. doi: 10.2337/db07-1344 · DOI
  9. Christiansen T, Richelsen B, Bruun JM. Monocyte chemoattractant pro- tein-1 is produced in isolated adipocytes, associated with adiposity and reduced after weight loss in morbid obese subjects. Int J Obes (Lond). 2005;29:146-150. doi: 10.1038/sj.ijo.0802839 · DOI
  10. Wu H, Perrard XD, Wang Q, Perrard JL, Polsani VR, Jones PH, Smith CW, Ballantyne CM. CD11c expression in adipose tissue and blood and its role in diet-induced obesity. Arterioscler Thromb Vasc Biol. 2010;30:186-192. doi: 10.1161/ATVBAHA.109.198044 · DOI
  11. Olefsky JM, Glass CK. Macrophages, inflammation, and insu- lin resistance. Annu Rev Physiol. 2010;72:219-246. doi: 10.1146/annurev-physiol-021909-135846 · DOI · Paper page
  12. Lumeng CN, DelProposto JB, Westcott DJ, Saltiel AR. Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes. Diabetes. 2008;57:3239-3246. doi: 10.2337/db08-0872 · DOI
  13. Cho KW, Zamarron BF, Muir LA, Singer K, Porsche CE, DelProposto JB, Geletka L, Meyer KA, O'Rourke RW, Lumeng CN. Adipose tissue dendritic cells are independent contributors to obesity-induced inflam- mation and insulin resistance. J Immunol. 2016;197:3650-3661. doi: 10.4049/jimmunol.1600820 · DOI
  14. Bertola A, Ciucci T, Rousseau D, Bourlier V, Duffaut C, Bonnafous S, Blin-Wakkach C, Anty R, Iannelli A, Gugenheim J, et al. Identification of adipose tissue dendritic cells correlated with obesity-associated insulin- resistance and inducing Th17 responses in mice and patients. Diabetes. 2012;61:2238-2247. doi: 10.2337/db11-1274 · DOI
  15. Kratz M, Coats BR, Hisert KB, Hagman D, Mutskov V, Peris E, Schoenfelt KQ, Kuzma JN, Larson I, Billing PS, et al. Metabolic dysfunction drives a mechanistically distinct proinflammatory phenotype in adipose tissue macro- phages. Cell Metab. 2014;20:614-625. doi: 10.1016/j.cmet.2014.08.010 · DOI
  16. Wentworth JM, Naselli G, Brown WA, Doyle L, Phipson B, Smyth GK, Wabitsch M, O'Brien PE, Harrison LC. Pro-inflammatory CD11c+CD206+ adipose tissue macrophages are associated with insulin resistance in human obesity. Diabetes. 2010;59:1648-1656. doi: 10.2337/db09-0287 · DOI
  17. Hill DA, Lim HW, Kim YH, Ho WY, Foong YH, Nelson VL, Nguyen HCB, Chegireddy K, Kim J, Habertheuer A, et al. Distinct macrophage populations direct inflammatory versus physiological changes in adi- pose tissue. Proc Natl Acad Sci U S A. 2018;115:E5096-E5105. doi: 10.1073/pnas.1802611115 · DOI · Paper page
  18. Xu X, Grijalva A, Skowronski A, van Eijk M, Serlie MJ, Ferrante AW Jr. Obe- sity activates a program of lysosomal-dependent lipid metabolism in adi- pose tissue macrophages independently of classic activation. Cell Metab. 2013;18:816-830. doi: 10.1016/j.cmet.2013.11.001 · DOI · Paper page
  19. McLaughlin T, Liu LF, Lamendola C, Shen L, Morton J, Rivas H, Winer D, Tolentino L, Choi O, Zhang H, et al. T-cell profile in adipose tis- sue is associated with insulin resistance and systemic inflammation in humans. Arterioscler Thromb Vasc Biol. 2014;34:2637-2643. doi: 10.1161/ATVBAHA.114.304636 · DOI
  20. García-Rubio J, León J, Redruello-Romero A, Pavón E, Cozar A, Tamayo F, Caba-Molina M, Salmerón J, Carazo Á. Cytometric analysis of adi- pose tissue reveals increments of adipocyte progenitor cells after weight loss induced by bariatric surgery. Sci Rep. 2018;8:15203. doi: 10.1038/s41598-018-33488-7 · DOI
  21. Deng T, Lyon CJ, Minze LJ, Lin J, Zou J, Liu JZ, Ren Y, Yin Z, Hamilton DJ, Reardon PR, et al. Class II major histocompatibility complex plays an essen- tial role in obesity-induced adipose inflammation. Cell Metab. 2013;17:411- 422. doi: 10.1016/j.cmet.2013.02.009 · DOI
  22. Nishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H, Ohsugi M, Otsu M, Hara K, Ueki K, Sugiura S, et al. CD8+ effector T cells contribute to mac- rophage recruitment and adipose tissue inflammation in obesity. Nat Med. 2009;15:914-920. doi: 10.1038/nm.1964 · DOI · Paper page
  23. Rocha VZ, Folco EJ, Sukhova G, Shimizu K, Gotsman I, Vernon AH, Libby P. Interferon-gamma, a Th1 cytokine, regulates fat inflammation: a role for adaptive immunity in obesity. Circ Res. 2008;103:467-476. doi: 10.1161/CIRCRESAHA.108.177105 · DOI
  24. Jiang E, Perrard XD, Yang D, Khan IM, Perrard JL, Smith CW, Ballantyne CM, Wu H. Essential role of CD11a in CD8+ T-cell accumulation and acti- vation in adipose tissue. Arterioscler Thromb Vasc Biol. 2014;34:34-43. doi: 10.1161/ATVBAHA.113.302077 · DOI
  25. Wang Q, Wu H. T Cells in Adipose Tissue: Critical Players in Immunome- tabolism. Front Immunol. 2018;9:2509. doi: 10.3389/fimmu.2018.02509 · DOI
  26. Khan IM, Dai Perrard XY, Perrard JL, Mansoori A, Smith CW, Wu H, Ballantyne CM. Attenuated adipose tissue and skeletal muscle inflammation in obese mice with combined CD4+ and CD8+ T cell deficiency. Atheroscle- rosis. 2014;233:419-428. doi: 10.1016/j.atherosclerosis.2014.01.011 · DOI
  27. Travers RL, Motta AC, Betts JA, Bouloumié A, Thompson D. The impact of adiposity on adipose tissue-resident lymphocyte activation in humans. Int J Obes (Lond). 2015;39:762-769. doi: 10.1038/ijo.2014.195 · DOI
  28. Winer S, Chan Y, Paltser G, Truong D, Tsui H, Bahrami J, Dorfman R, Wang Y, Zielenski J, Mastronardi F, et al. Normalization of obesity-associated insu- lin resistance through immunotherapy. Nat Med. 2009;15:921-929. doi: 10.1038/nm.2001 · DOI · Paper page
  29. Cho KW, Morris DL, DelProposto JL, Geletka L, Zamarron B, Martinez-Santibanez G, Meyer KA, Singer K, O'Rourke RW, Lumeng CN. An MHC II-dependent activation loop between adipose tissue macro- phages and CD4+ T cells controls obesity-induced inflammation. Cell Rep. 2014;9:605-617. doi: 10.1016/j.celrep.2014.09.004 · DOI
  30. Khan IM, Perrard XY, Brunner G, Lui H, Sparks LM, Smith SR, Wang X, Shi ZZ, Lewis DE, Wu H, et al. Intermuscular and perimuscular fat expansion in obesity correlates with skeletal muscle T cell and macrophage infiltra- tion and insulin resistance. Int J Obes (Lond). 2015;39:1607-1618. doi: 10.1038/ijo.2015.104 · DOI
  31. Yang H, Youm YH, Vandanmagsar B, Ravussin A, Gimble JM, Greenway F, Stephens JM, Mynatt RL, Dixit VD. Obesity increases the production of pro- inflammatory mediators from adipose tissue T cells and compromises TCR repertoire diversity: implications for systemic inflammation and insulin resis- tance. J Immunol. 2010;185:1836-1845. doi: 10.4049/jimmunol.1000021 · DOI
  32. Ilan Y, Maron R, Tukpah AM, Maioli TU, Murugaiyan G, Yang K, Wu HY, Weiner HL. Induction of regulatory T cells decreases adipose inflammation and alleviates insulin resistance in ob/ob mice. Proc Natl Acad Sci U S A. 2010;107:9765-9770. doi: 10.1073/pnas.0908771107 · DOI
  33. Mehta P, Nuotio-Antar AM, Smith CW. γδ T cells promote inflammation and insulin resistance during high fat diet-induced obesity in mice. J Leukoc Biol. 2015;97:121-134. doi: 10.1189/jlb.3A0414-211RR · DOI
  34. Kalathookunnel Antony A, Lian Z, Wu H. T Cells in Adipose Tissue in Aging. Front Immunol. 2018;9:2945. doi: 10.3389/fimmu.2018.02945 · DOI
  35. Ohmura K, Ishimori N, Ohmura Y, Tokuhara S, Nozawa A, Horii S, Andoh Y, Fujii S, Iwabuchi K, Onoé K, et al. Natural killer T cells are involved in adipose tissues inflammation and glucose intolerance in diet-induced obese mice. Arterioscler Thromb Vasc Biol. 2010;30:193-199. doi: 10.1161/ATVBAHA.109.198614 · DOI
  36. Wu L, Parekh VV, Gabriel CL, Bracy DP, Marks-Shulman PA, Tamboli RA, Kim S, Mendez-Fernandez YV, Besra GS, Lomenick JP, et al. Activation of invariant natural killer T cells by lipid excess promotes tissue inflammation, insulin resistance, and hepatic steatosis in obese mice. Proc Natl Acad Sci U S A. 2012;109:E1143-E1152. doi: 10.1073/pnas.1200498109 · DOI
  37. Satoh M, Andoh Y, Clingan CS, Ogura H, Fujii S, Eshima K, Nakayama T, Taniguchi M, Hirata N, Ishimori N, et al. Type II NKT cells stimulate diet-induced obesity by mediating adipose tissue inflammation, ste- atohepatitis and insulin resistance. PLoS One. 2012;7:e30568. doi: 10.1371/journal.pone.0030568 · DOI
  38. Lynch L, Nowak M, Varghese B, Clark J, Hogan AE, Toxavidis V, Balk SP, O'Shea D, O'Farrelly C, Exley MA. Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production. Immunity. 2012;37:574-587. doi: 10.1016/j.immuni.2012.06.016 · DOI
  39. Huh JY, Park J, Kim JI, Park YJ, Lee YK, Kim JB. Deletion of CD1d in Adi- pocytes Aggravates Adipose Tissue Inflammation and Insulin Resistance in Obesity. Diabetes. 2017;66:835-847. doi: 10.2337/db16-1122 · DOI
  40. Huh JY, Park YJ, Kim JB. Adipocyte CD1d determines adipose inflam- mation and insulin resistance in obesity. Adipocyte. 2018;7:129-136. doi: 10.1080/21623945.2018.1440928 · DOI
  41. Winer DA, Winer S, Shen L, Wadia PP, Yantha J, Paltser G, Tsui H, Wu P, Davidson MG, Alonso MN, et al. B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nat Med. 2011;17:610-617. doi: 10.1038/nm.2353 · DOI · Paper page
  42. McDonnell ME, Ganley-Leal LM, Mehta A, Bigornia SJ, Mott M, Rehman Q, Farb MG, Hess DT, Joseph L, Gokce N, et al. B lymphocytes in human subcutaneous adipose crown-like structures. Obesity (Silver Spring). 2012;20:1372-1378. doi: 10.1038/oby.2012.54 · DOI
  43. Harmon DB, Srikakulapu P, Kaplan JL, Oldham SN, McSkimming C, Garmey JC, Perry HM, Kirby JL, Prohaska TA, Gonen A, et al. Protective Role for B-1b B Cells and IgM in Obesity-Associated Inflammation, Glucose Intoler- ance, and Insulin Resistance. Arterioscler Thromb Vasc Biol. 2016;36:682- 691. doi: 10.1161/ATVBAHA.116.307166 · DOI
  44. Nishimura S, Manabe I, Takaki S, Nagasaki M, Otsu M, Yamashita H, Sugita J, Yoshimura K, Eto K, Komuro I, et al. Adipose Natural Regulatory B Cells Negatively Control Adipose Tissue Inflammation. Cell Metab. 2013;18:759- 766. doi: 10.1016/j.cmet.2013.09.017 · DOI · Paper page
  45. Elgazar-Carmon V, Rudich A, Hadad N, Levy R. Neutrophils transiently infil- trate intra-abdominal fat early in the course of high-fat feeding. J Lipid Res. 2008;49:1894-1903. doi: 10.1194/jlr.M800132-JLR200 · DOI
  46. Talukdar S, Oh DY, Bandyopadhyay G, Li D, Xu J, McNelis J, Lu M, Li P, Yan Q, Zhu Y, et al. Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Nat Med. 2012;18:1407-1412. doi: 10.1038/nm.2885 · DOI
  47. Wang Q, Xie Z, Zhang W, Zhou J, Wu Y, Zhang M, Zhu H, Zou MH. Myelo- peroxidase deletion prevents high-fat diet-induced obesity and insulin resis- tance. Diabetes. 2014;63:4172-4185. doi: 10.2337/db14-0026 · DOI
  48. Hadad N, Burgazliev O, Elgazar-Carmon V, Solomonov Y, Wueest S, Item F, Konrad D, Rudich A, Levy R. Induction of cytosolic phospholipase a2α is required for adipose neutrophil infiltration and hepatic insulin resistance early in the course of high-fat feeding. Diabetes. 2013;62:3053-3063. doi: 10.2337/db12-1300 · DOI
  49. Wu D, Molofsky AB, Liang HE, Ricardo-Gonzalez RR, Jouihan HA, Bando JK, Chawla A, Locksley RM. Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science. 2011;332:243-247. doi: 10.1126/science.1201475 · DOI
  50. Bolus WR, Peterson KR, Hubler MJ, Kennedy AJ, Gruen ML, Hasty AH. Elevating adipose eosinophils in obese mice to physiologically normal lev- els does not rescue metabolic impairments. Mol Metab. 2018;8:86-95. doi: 10.1016/j.molmet.2017.12.004 · DOI
  51. Bolus WR, Hasty AH. Contributions of innate type 2 inflammation to adipose function. J Lipid Res. 2019;60:1698-1709. doi: 10.1194/jlr.R085993 · DOI
  52. Bolus WR, Gutierrez DA, Kennedy AJ, Anderson-Baucum EK, Hasty AH. CCR2 deficiency leads to increased eosinophils, alternative macrophage activation, and type 2 cytokine expression in adipose tissue. J Leukoc Biol. 2015;98:467-477. doi: 10.1189/jlb.3HI0115-018R · DOI
  53. Fabbiano S, Suárez-Zamorano N, Rigo D, Veyrat-Durebex C, Stevanovic Dokic A, Colin DJ, Trajkovski M. Caloric restriction leads to browning of white adipose tissue through type 2 immune signaling. Cell Metab. 2016;24:434-446. doi: 10.1016/j.cmet.2016.07.023 · DOI
  54. Suárez-Zamorano N, Fabbiano S, Chevalier C, Stojanović O, Colin DJ, Stevanović A, Veyrat-Durebex C, Tarallo V, Rigo D, Germain S, et al. Micro- biota depletion promotes browning of white adipose tissue and reduces obesity. Nat Med. 2015;21:1497-1501. doi: 10.1038/nm.3994 · DOI · Paper page
  55. Molofsky AB, Nussbaum JC, Liang HE, Van Dyken SJ, Cheng LE, Mohapatra A, Chawla A, Locksley RM. Innate lymphoid type 2 cells sustain visceral adi- pose tissue eosinophils and alternatively activated macrophages. J Exp Med. 2013;210:535-549. doi: 10.1084/jem.20121964 · DOI
  56. Rao RR, Long JZ, White JP, Svensson KJ, Lou J, Lokurkar I, Jedrychowski MP, Ruas JL, Wrann CD, Lo JC, et al. Meteorin-like is a hormone that regu- lates immune-adipose interactions to increase beige fat thermogenesis. Cell. 2014;157:1279-1291. doi: 10.1016/j.cell.2014.03.065 · DOI · Paper page
  57. Qiu Y, Nguyen KD, Odegaard JI, Cui X, Tian X, Locksley RM, Palmiter RD, Chawla A. Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat. Cell. 2014;157:1292- 1308. doi: 10.1016/j.cell.2014.03.066 · DOI
  58. Einwallner E, Kiefer FW, Di Caro G, Orthofer M, Witzeneder N, Hörmann G, Itariu B, Zeyda M, Penninger JM, Stulnig TM, et al. Mast cells are not associ- ated with systemic insulin resistance. Eur J Clin Invest. 2016;46:911-919. doi: 10.1111/eci.12675 · DOI
  59. Gurung P, Moussa K, Adams-Huet B, Devaraj S, Jialal I. Increased mast cell abundance in adipose tissue of metabolic syndrome: relevance to the proin- flammatory state and increased adipose tissue fibrosis. Am J Physiol Endo- crinol Metab. 2019;316:E504-E509. doi: 10.1152/ajpendo.00462.2018 · DOI
  60. Lee BC, Kim MS, Pae M, Yamamoto Y, Eberlé D, Shimada T, Kamei N, Park HS, Sasorith S, Woo JR, et al. Adipose natural killer cells regulate adipose tissue macrophages to promote insulin resistance in obesity. Cell Metab. 2016;23:685-698. doi: 10.1016/j.cmet.2016.03.002 · DOI
  61. Wensveen FM, Jelenčić V, Valentić S, Šestan M, Wensveen TT, Theurich S, Glasner A, Mendrila D, Štimac D, Wunderlich FT, et al. NK cells link obesity- induced adipose stress to inflammation and insulin resistance. Nat Immunol. 2015;16:376-385. doi: 10.1038/ni.3120 · DOI
  62. O'Rourke RW, Meyer KA, Neeley CK, Gaston GD, Sekhri P, Szumowski M, Zamarron B, Lumeng CN, Marks DL. Systemic NK cell ablation attenuates intra-abdominal adipose tissue macrophage infiltration in murine obesity. Obesity (Silver Spring). 2014;22:2109-2114. doi: 10.1002/oby.20823 · DOI
  63. O'Sullivan TE, Rapp M, Fan X, Weizman OE, Bhardwaj P, Adams NM, Walzer T, Dannenberg AJ, Sun JC. Adipose-resident group 1 innate lymphoid cells promote obesity-associated insulin resistance. Immunity. 2016;45:428- 441. doi: 10.1016/j.immuni.2016.06.016 · DOI · Paper page
  64. Wang H, Shen L, Sun X, Liu F, Feng W, Jiang C, Chu X, Ye X, Jiang C, Wang Y, et al. Adipose group 1 innate lymphoid cells promote adipose tissue fibrosis and diabetes in obesity. Nat Commun. 2019;10:3254. doi: 10.1038/s41467-019-11270-1 · DOI
  65. Boulenouar S, Michelet X, Duquette D, Alvarez D, Hogan AE, Dold C, O'Connor D, Stutte S, Tavakkoli A, Winters D, et al. Adipose type one innate lymphoid cells regulate macrophage homeostasis through targeted cyto- toxicity. Immunity. 2017;46:273-286. doi: 10.1016/j.immuni.2017.01.008 · DOI
  66. Brestoff JR, Kim BS, Saenz SA, Stine RR, Monticelli LA, Sonnenberg GF, Thome JJ, Farber DL, Lutfy K, Seale P, et al. Group 2 innate lymphoid cells promote beiging of white adipose tissue and limit obesity. Nature. 2015;519:242-246. doi: 10.1038/nature14115 · DOI · Paper page
  67. Molofsky AB, Van Gool F, Liang HE, Van Dyken SJ, Nussbaum JC, Lee J, Bluestone JA, Locksley RM. Interleukin-33 and Interferon- γ Counter-Regulate Group 2 Innate Lymphoid Cell Activation dur- ing Immune Perturbation. Immunity. 2015;43:161-174. doi: 10.1016/j.immuni.2015.05.019 · DOI
  68. Boettcher M, Machann J, Stefan N, Thamer C, Häring HU, Claussen CD, Fritsche A, Schick F. Intermuscular adipose tissue (IMAT): association with other adipose tissue compartments and insulin sensitivity. J Magn Reson Imaging. 2009;29:1340-1345. doi: 10.1002/jmri.21754 · DOI · Paper page
  69. Zoico E, Rossi A, Di Francesco V, Sepe A, Olioso D, Pizzini F, Fantin F, Bosello O, Cominacini L, Harris TB, et al. Adipose tissue infiltration in skeletal muscle of healthy elderly men: relationships with body composition, insulin resistance, and inflammation at the systemic and tissue level. J Gerontol A Biol Sci Med Sci. 2010;65:295-299. doi: 10.1093/gerona/glp155 · DOI
  70. Wang J, Perrard XD, Perrard JL, Mukherjee A, Rosales C, Chen Y, Smith CW, Pownall HJ, Ballantyne CM, Wu H. ApoE and the role of very low density lipoproteins in adipose tissue inflammation. Atherosclerosis. 2012;223:342-349. doi: 10.1016/j.atherosclerosis.2012.06.003 · DOI
  71. Fink LN, Costford SR, Lee YS, Jensen TE, Bilan PJ, Oberbach A, Blüher M, Olefsky JM, Sams A, Klip A. Pro-inflammatory macrophages increase in skeletal muscle of high fat-fed mice and correlate with metabolic risk markers in humans. Obesity (Silver Spring). 2014;22:747-757. doi: 10.1002/oby.20615 · DOI
  72. Brake DK, Smith EO, Mersmann H, Smith CW, Robker RL. ICAM-1 expres- sion in adipose tissue: effects of diet-induced obesity in mice. Am J Physiol Cell Physiol. 2006;291:C1232-C1239. doi: 10.1152/ajpcell.00008.2006 · DOI
  73. Wu H, Gower RM, Wang H, Perrard XY, Ma R, Bullard DC, Burns AR, Paul A, Smith CW, Simon SI, et al. Functional role of CD11c+ mono- cytes in atherogenesis associated with hypercholesterolemia. Circulation. 2009;119:2708-2717. doi: 10.1161/CIRCULATIONAHA.108.823740 100. Xu L, Dai Perrard X, Perrard JL, Yang D, Xiao X, Teng BB, Simon SI, Ballantyne CM, Wu H. Foamy monocytes form early and contribute to na- scent atherosclerosis in mice with hypercholesterolemia. Arterioscler Thromb Vasc Biol. 2015;35:1787-1797. doi: 10.1161/ATVBAHA.115.305609 101. Oh DY, Morinaga H, Talukdar S, Bae EJ, Olefsky JM. Increased macrophage migration into adipose tissue in obese mice. Diabetes. 2012;61:346-354. doi: 10.2337/db11-0860 102. · DOI
  74. Gong Z, Zhang X, Su K, Jiang R, Sun Z, Chen W, Forno E, Goetzman ES, Wang J, Dong HH, et al. Deficiency in AIM2 induces inflammation and adi- pogenesis in white adipose tissue leading to obesity and insulin resistance. Diabetologia. 2019;62:2325-2339 103.
  75. Ramkhelawon B, Hennessy EJ, Ménager M, Ray TD, Sheedy FJ, Hutchison S, Wanschel A, Oldebeken S, Geoffrion M, Spiro W, et al. Netrin-1 promotes adipose tissue macrophage retention and insulin resistance in obesity. Nat Med. 2014;20:377-384. doi: 10.1038/nm.3467 104. · DOI
  76. Keophiphath M, Rouault C, Divoux A, Clément K, Lacasa D. CCL5 promotes macrophage recruitment and survival in human adipose tissue. Arterioscler Thromb Vasc Biol. 2010;30:39-45. doi: 10.1161/ATVBAHA.109.197442 105. · DOI
  77. Kitade H, Sawamoto K, Nagashimada M, Inoue H, Yamamoto Y, Sai Y, Takamura T, Yamamoto H, Miyamoto K, Ginsberg HN, et al. CCR5 plays a critical role in obesity-induced adipose tissue inflammation and insulin resistance by regulating both macrophage recruitment and M1/M2 status. Diabetes. 2012;61:1680-1690. doi: 10.2337/db11-1506 106. · DOI
  78. Weisberg SP, Hunter D, Huber R, Lemieux J, Slaymaker S, Vaddi K, Charo I, Leibel RL, Ferrante AW Jr. CCR2 modulates inflammatory and meta- bolic effects of high-fat feeding. J Clin Invest. 2006;116:115-124. doi: 10.1172/JCI24335 108. · DOI
  79. Li P, Oh DY, Bandyopadhyay G, Lagakos WS, Talukdar S, Osborn O, Johnson A, Chung H, Maris M, Ofrecio JM, et al. LTB4 promotes insu- lin resistance in obese mice by acting on macrophages, hepatocytes and myocytes. Nat Med. 2015;21:239-247. doi: 10.1038/nm.3800 109. · DOI
  80. Féral CC, Neels JG, Kummer C, Slepak M, Olefsky JM, Ginsberg MH. Blockade of alpha4 integrin signaling ameliorates the metabolic conse- quences of high-fat diet-induced obesity. Diabetes. 2008;57:1842-1851. doi: 10.2337/db07-1751 110. · DOI
  81. Russo HM, Wickenheiser KJ, Luo W, Ohman MK, Franchi L, Wright AP, Bodary PF, Núñez G, Gabriel N, Eitzman DT. P-selectin glycoprotein li- gand-1 regulates adhesive properties of the endothelium and leuko- cyte trafficking into adipose tissue. Circ Res. 2010;107:388-397. doi: 10.1161/CIRCRESAHA.110.218651 111. · DOI
  82. Amano SU, Cohen JL, Vangala P, Tencerova M, Nicoloro SM, Yawe JC, Shen Y, Czech MP, Aouadi M. Local proliferation of macrophages con- tributes to obesity-associated adipose tissue inflammation. Cell Metab. 2014;19:162-171. doi: 10.1016/j.cmet.2013.11.017 112. · DOI
  83. Haase J, Weyer U, Immig K, Klöting N, Blüher M, Eilers J, Bechmann I, Gericke M. Local proliferation of macrophages in adipose tissue dur- ing obesity-induced inflammation. Diabetologia. 2014;57:562-571. doi: 10.1007/s00125-013-3139-y 113. · DOI
  84. Uysal KT, Wiesbrock SM, Marino MW, Hotamisligil GS. Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature. 1997;389:610-614. doi: 10.1038/39335 114. · DOI
  85. Dobrian AD, Galkina EV, Ma Q, Hatcher M, Aye SM, Butcher MJ, Ma K, Haynes BA, Kaplan MH, Nadler JL. STAT4 deficiency reduces obesity- induced insulin resistance and adipose tissue inflammation. Diabetes. 2013;62:4109-4121. doi: 10.2337/db12-1275 115. · DOI
  86. Arkan MC, Hevener AL, Greten FR, Maeda S, Li ZW, Long JM, Wynshaw-Boris A, Poli G, Olefsky J, Karin M. IKK-beta links inflammation to obesity-induced insulin resistance. Nat Med. 2005;11:191-198. doi: 10.1038/nm1185 116. · DOI
  87. Chiang SH, Bazuine M, Lumeng CN, Geletka LM, Mowers J, White NM, Ma JT, Zhou J, Qi N, Westcott D, et al. The protein kinase IKKepsilon regulates energy balance in obese mice. Cell. 2009;138:961-975. doi: 10.1016/j.cell.2009.06.046 117. · DOI
  88. Braster Q, Silvestre-Roig C, Hartwig H, Kusters P, Aarts S, den Toom M, Gallo RL, Weber C, Lutgens E, Soehnlein O. Cathelicidin regulates myeloid cell accumulation in adipose tissue and promotes insulin re- sistance during obesity. Thromb Haemost. 2016;115:1237-1239. doi: 10.1160/TH16-02-0112 119. · DOI
  89. Rana BMJ, Jou E, Barlow JL, Rodriguez-Rodriguez N, Walker JA, Knox C, Jolin HE, Hardman CS, Sivasubramaniam M, Szeto A, et al. A stromal cell niche sustains ILC2-mediated type-2 conditioning in adipose tissue. J Exp Med. 2019;216:1999-2009. doi: 10.1084/jem.20190689 120. Wolf D, Jehle F, Michel NA, Bukosza EN, Rivera J, Chen YC, Hoppe N, Dufner B, Rodriguez AO, Colberg C, et al. Coinhibitory suppres- sion of T cell activation by CD40 protects against obesity and adipose tissue inflammation in mice. Circulation. 2014;129:2414-2425. doi: 10.1161/CIRCULATIONAHA.113.008055 121. · DOI
  90. Chatzigeorgiou A, Seijkens T, Zarzycka B, Engel D, Poggi M, van den Berg S, van den Berg S, Soehnlein O, Winkels H, Beckers L, et al. Blocking CD40-TRAF6 signaling is a therapeutic target in obesity-associated in- sulin resistance. Proc Natl Acad Sci U S A. 2014;111:2686-2691. doi: 10.1073/pnas.1400419111 122. · DOI
  91. Zhong J, Rao X, Braunstein Z, Taylor A, Narula V, Hazey J, Mikami D, Needleman B, Rutsky J, Sun Q, et al. T-cell costimulation protects obesity-induced adipose inflammation and insulin resistance. Diabetes. 2014;63:1289-1302. doi: 10.2337/db13-1094 123. · DOI
  92. Poggi M, Engel D, Christ A, Beckers L, Wijnands E, Boon L, Driessen A, Cleutjens J, Weber C, Gerdes N, et al. CD40L deficiency amelio- rates adipose tissue inflammation and metabolic manifestations of obe- sity in mice. Arterioscler Thromb Vasc Biol. 2011;31:2251-2260. doi: 10.1161/ATVBAHA.111.231357 124. Liu B, Yu H, Sun G, Sun X, Jin H, Zhang C, Shi W, Tian D, Liu K, Xu H, et al. OX40 promotes obesity-induced adipose inflammation and insulin resistance. Cell Mol Life Sci. 2017;74:3827-3840. doi: 10.1007/s00018-017-2552-7 125. · DOI
  93. Oldenhove G, Boucquey E, Taquin A, Acolty V, Bonetti L, Ryffel B, Le Bert M, Englebert K, Boon L, Moser M. PD-1 Is Involved in the Dysregulation of Type 2 Innate Lymphoid Cells in a Murine Model of Obesity. Cell Rep. 2018;25:2053-2060.e4. doi: 10.1016/j.celrep.2018.10.091 126. Wang Q, Perrard XD, Perrard JL, Mansoori A, Raya JL, Hoogeveen R, Smith CW, Ballantyne CM, Wu H. Differential effect of weight loss with low- fat diet or high-fat diet restriction on inflammation in the liver and adipose tissue of mice with diet-induced obesity. Atherosclerosis. 2011;219:100- 108. doi: 10.1016/j.atherosclerosis.2011.07.025 127. Li P, Lu M, Nguyen MT, Bae EJ, Chapman J, Feng D, Hawkins M, Pessin JE, Sears DD, Nguyen AK, et al. Functional heterogeneity of CD11c-positive adipose tissue macrophages in diet-induced obese mice. J Biol Chem. 2010;285:15333-15345. doi: 10.1074/jbc.M110.100263 128. · DOI
  94. Han MS, Jung DY, Morel C, Lakhani SA, Kim JK, Flavell RA, Davis RJ. JNK expression by macrophages promotes obesity-induced insu- lin resistance and inflammation. Science. 2013;339:218-222. doi: 10.1126/science.1227568 130. · DOI
  95. Vandanmagsar B, Youm YH, Ravussin A, Galgani JE, Stadler K, Mynatt RL, Ravussin E, Stephens JM, Dixit VD. The NLRP3 inflammasome in- stigates obesity-induced inflammation and insulin resistance. Nat Med. 2011;17:179-188. doi: 10.1038/nm.2279 131. · DOI
  96. Wen H, Gris D, Lei Y, Jha S, Zhang L, Huang MT, Brickey WJ, Ting JP. Fatty acid-induced NLRP3-ASC inflammasome activation interferes with insulin signaling. Nat Immunol. 2011;12:408-415. doi: 10.1038/ni.2022 132. · DOI
  97. Ye J, Gao Z, Yin J, He Q. Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice. Am J Physiol Endocrinol Metab. 2007;293:E1118- E1128. doi: 10.1152/ajpendo.00435.2007 134. · DOI
  98. Gonzalez FJ, Xie C, Jiang C. The role of hypoxia-inducible fac- tors in metabolic diseases. Nat Rev Endocrinol. 2018;15:21-32. doi: 10.1038/s41574-018-0096-z 136. · DOI
  99. Jiang C, Qu A, Matsubara T, Chanturiya T, Jou W, Gavrilova O, Shah YM, Gonzalez FJ. Disruption of hypoxia-inducible factor 1 in adipocytes im- proves insulin sensitivity and decreases adiposity in high-fat diet-fed mice. Diabetes. 2011;60:2484-2495. doi: 10.2337/db11-0174 137. · DOI
  100. Snodgrass RG, Boß M, Zezina E, Weigert A, Dehne N, Fleming I, Brüne B, Namgaladze D. Hypoxia Potentiates Palmitate-induced Pro-inflammatory Activation of Primary Human Macrophages. J Biol Chem. 2016;291:413- 424. doi: 10.1074/jbc.M115.686709 139. O'Rourke RW, White AE, Metcalf MD, Olivas AS, Mitra P, Larison WG, Cheang EC, Varlamov O, Corless CL, Roberts CT Jr, et al. Hypoxia-induced inflam- matory cytokine secretion in human adipose tissue stromovascular cells. Diabetologia. 2011;54:1480-1490. doi: 10.1007/s00125-011-2103-y 140. · DOI
  101. Tilg H, Zmora N, Adolph TE, Elinav E. The intestinal microbiota fuel- ling metabolic inflammation. Nat Rev Immunol. 2020;20:40-54. doi: 10.1038/s41577-019-0198-4 141. · DOI
  102. Bleau C, Karelis AD, St-Pierre DH, Lamontagne L. Crosstalk between intestinal microbiota, adipose tissue and skeletal muscle as an early event in systemic low-grade inflammation and the development of obe- sity and diabetes. Diabetes Metab Res Rev. 2015;31:545-561. doi: 10.1002/dmrr.2617 142. · DOI
  103. Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007;56:1761-1772. doi: 10.2337/db06-1491 143. · DOI
  104. Pendyala S, Walker JM, Holt PR. A high-fat diet is associated with endo- toxemia that originates from the gut. Gastroenterology. 2012;142:1100- 1101.e2. doi: 10.1053/j.gastro.2012.01.034 144. Mehta NN, McGillicuddy FC, Anderson PD, Hinkle CC, Shah R, Pruscino L, Tabita-Martinez J, Sellers KF, Rickels MR, Reilly MP. Experimental en- dotoxemia induces adipose inflammation and insulin resistance in humans. Diabetes. 2010;59:172-181. doi: 10.2337/db09-0367 145. · DOI
  105. Osto M, Zini E, Franchini M, Wolfrum C, Guscetti F, Hafner M, Ackermann M, Reusch CE, Lutz TA. Subacute endotoxemia induces adipose inflamma- tion and changes in lipid and lipoprotein metabolism in cats. Endocrinology. 2011;152:804-815. doi: 10.1210/en.2010-0999 146. · DOI
  106. Shimobayashi M, Albert V, Woelnerhanssen B, Frei IC, Weissenberger D, Meyer-Gerspach AC, Clement N, Moes S, Colombi M, Meier JA, et al. Insulin resistance causes inflammation in adipose tissue. J Clin Invest. 2018;128:1538-1550. doi: 10.1172/JCI96139 148. · DOI
  107. Stolarczyk E, Vong CT, Perucha E, Jackson I, Cawthorne MA, Wargent ET, Powell N, Canavan JB, Lord GM, Howard JK. Improved insulin sen- sitivity despite increased visceral adiposity in mice deficient for the im- mune cell transcription factor T-bet. Cell Metab. 2013;17:520-533. doi: 10.1016/j.cmet.2013.02.019 151. · DOI
  108. Gutierrez DA, Muralidhar S, Feyerabend TB, Herzig S, Rodewald HR. Hematopoietic Kit Deficiency, rather than Lack of Mast Cells, Protects Mice from Obesity and Insulin Resistance. Cell Metab. 2015;21:678-691. doi: 10.1016/j.cmet.2015.04.013 152. · DOI
  109. Aouadi M, Vangala P, Yawe JC, Tencerova M, Nicoloro SM, Cohen JL, Shen Y, Czech MP. Lipid storage by adipose tissue macrophages regulates sys- temic glucose tolerance. Am J Physiol Endocrinol Metab. 2014;307:E374- E383. doi: 10.1152/ajpendo.00187.2014 153. · DOI
  110. Koliwad SK, Streeper RS, Monetti M, Cornelissen I, Chan L, Terayama K, Naylor S, Rao M, Hubbard B, Farese RV Jr. DGAT1-dependent tria- cylglycerol storage by macrophages protects mice from diet-induced in- sulin resistance and inflammation. J Clin Invest. 2010;120:756-767. doi: 10.1172/JCI36066 154. · DOI
  111. Villarroya F, Cereijo R, Villarroya J, Gavaldà-Navarro A, Giralt M. Toward an Understanding of How Immune Cells Control Brown and Beige Adipobiology. Cell Metab. 2018;27:954-961. doi: 10.1016/j.cmet.2018.04.006 155. · DOI
  112. Nguyen KD, Qiu Y, Cui X, Goh YP, Mwangi J, David T, Mukundan L, Brombacher F, Locksley RM, Chawla A. Alternatively activated macro- phages produce catecholamines to sustain adaptive thermogenesis. Nature. 2011;480:104-108. doi: 10.1038/nature10653 156. · DOI
  113. Fischer K, Ruiz HH, Jhun K, Finan B, Oberlin DJ, van der Heide V, Kalinovich AV, Petrovic N, Wolf Y, Clemmensen C, et al. Alternatively ac- tivated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis. Nat Med. 2017;23:623-630. doi: 10.1038/nm.4316 157. · DOI
  114. Lee MW, Odegaard JI, Mukundan L, Qiu Y, Molofsky AB, Nussbaum JC, Yun K, Locksley RM, Chawla A. Activated type 2 innate lym- phoid cells regulate beige fat biogenesis. Cell. 2015;160:74-87. doi: 10.1016/j.cell.2014.12.011 158. · DOI
  115. Sakamoto T, Nitta T, Maruno K, Yeh YS, Kuwata H, Tomita K, Goto T, Takahashi N, Kawada T. Macrophage infiltration into obese adipose tissues suppresses the induction of UCP1 level in mice. Am J Physiol Endocrinol Metab. 2016;310:E676-E687. doi: 10.1152/ajpendo.00028.2015 159. · DOI
  116. Okla M, Zaher W, Alfayez M, Chung S. Inhibitory Effects of Toll-Like Receptor 4, NLRP3 Inflammasome, and Interleukin-1beta on White Adipocyte Browning. Inflammation. 2017;41:626-642 160.
  117. Moisan A, Lee YK, Zhang JD, Hudak CS, Meyer CA, Prummer M, Zoffmann S, Truong HH, Ebeling M, Kiialainen A, et al. White-to-brown metabolic con- version of human adipocytes by JAK inhibition. Nat Cell Biol. 2015;17:57- 67. doi: 10.1038/ncb3075 162. · DOI
  118. Koh EH, Chernis N, Saha PK, Xiao L, Bader DA, Zhu B, Rajapakshe K, Hamilton MP, Liu X, Perera D, et al. miR-30a Remodels Subcutaneous Adipose Tissue Inflammation to Improve Insulin Sensitivity in Obesity. Diabetes. 2018;67:2541-2553. doi: 10.2337/db17-1378 163. · DOI
  119. Moysidou M, Karaliota S, Kodela E, Salagianni M, Koutmani Y, Katsouda A, Kodella K, Tsakanikas P, Ourailidou S, Andreakos E, et al. CD8+ T cells in beige adipogenesis and energy homeostasis. JCI Insight. 2018;3:95456. 164. Giordano A, Frontini A, Cinti S. Convertible visceral fat as a therapeu- tic target to curb obesity. Nat Rev Drug Discov. 2016;15:405-424. doi: 10.1038/nrd.2016.31 165 · DOI
  120. Rajbhandari P, Thomas BJ, Feng AC, Hong C, Wang J, Vergnes L, Sallam T, Wang B, Sandhu J, Seldin MM, et al. IL-10 Signaling Remodels Adipose Chromatin Architecture to Limit Thermogenesis and Energy Expenditure. Cell. 2018;172:218-233.e17. doi: 10.1016/j.cell.2017.11.019 166. · DOI
  121. Pirzgalska RM, Seixas E, Seidman JS, Link VM, Sánchez NM, Mahú I, Mendes R, Gres V, Kubasova N, Morris I, et al. Sympathetic neuron-asso- ciated macrophages contribute to obesity by importing and metabolizing norepinephrine. Nat Med. 2017;23:1309-1318. doi: 10.1038/nm.4422 167. · DOI
  122. Zhang X, Wang X, Yin H, Zhang L, Feng A, Zhang QX, Lin Y, Bao B, Hernandez LL, Shi GP, et al. Functional inactivation of mast cells enhances subcutaneous adipose tissue browning in mice. Cell Rep. 2019;28:792- 803 e794. 168. Finlin BS, Confides AL, Zhu B, Boulanger MC, Memetimin H, Taylor KW, Johnson ZR, Westgate PM, Dupont-Versteegden EE, Kern PA. Adipose tissue mast cells promote human adipose beiging in response to cold. Sci Rep. 2019;9:8658. doi: 10.1038/s41598-019-45136-9 169. · DOI
  123. Marcelin G, Silveira ALM, Martins LB, Ferreira AV, Clément K. Deciphering the cellular interplays underlying obesity-induced adipose tissue fibrosis. J Clin Invest. 2019;129:4032-4040. doi: 10.1172/JCI129192 173. · DOI
  124. Strissel KJ, Stancheva Z, Miyoshi H, Perfield JW II, DeFuria J, Jick Z, Greenberg AS, Obin MS. Adipocyte death, adipose tissue remodel- ing, and obesity complications. Diabetes. 2007;56:2910-2918. doi: 10.2337/db07-0767 174. · DOI
  125. Hueso L, Ortega R, Selles F, Wu-Xiong NY, Ortega J, Civera M, Ascaso JF, Sanz MJ, Real JT, Piqueras L. Upregulation of angiostatic chemokines IP-10/CXCL10 and I-TAC/CXCL11 in human obesity and their implication for adipose tissue angiogenesis. Int J Obes (Lond). 2018;42:1406-1417. doi: 10.1038/s41366-018-0102-5 175. · DOI
  126. Hirai S, Ohyane C, Kim YI, Lin S, Goto T, Takahashi N, Kim CS, Kang J, Yu R, Kawada T. Involvement of mast cells in adipose tissue fi- brosis. Am J Physiol Endocrinol Metab. 2014;306:E247-E255. doi: 10.1152/ajpendo.00056.2013 176. · DOI
  127. Donath MY, Dinarello CA, Mandrup-Poulsen T. Targeting innate immune mediators in type 1 and type 2 diabetes. Nat Rev Immunol. 2019;19:734- 746. doi: 10.1038/s41577-019-0213-9 177. · DOI
  128. Goldfine AB, Shoelson SE. Therapeutic approaches targeting inflam- mation for diabetes and associated cardiovascular risk. J Clin Invest. 2017;127:83-93. doi: 10.1172/JCI88884 178. · DOI
  129. Fleischman A, Shoelson SE, Bernier R, Goldfine AB. Salsalate improves glycemia and inflammatory parameters in obese young adults. Diabetes Care. 2008;31:289-294. doi: 10.2337/dc07-1338 179. · DOI
  130. Goldfine AB, Silver R, Aldhahi W, Cai D, Tatro E, Lee J, Shoelson SE. Use of salsalate to target inflammation in the treatment of insulin resistance and type 2 diabetes. Clin Transl Sci. 2008;1:36-43. doi: 10.1111/j.1752-8062.2008.00026.x 180. Faghihimani E, Aminorroaya A, Rezvanian H, Adibi P, Ismail-Beigi F, Amini M. Reduction of insulin resistance and plasma glucose level by salsalate treatment in persons with prediabetes. Endocr Pract. 2012;18:826-833. doi: 10.4158/EP12064.OR 181. · DOI
  131. de Rotte MC, de Jong PH, den Boer E, Pluijm SM, Özcan B, Weel AE, Lindemans J, Hazes JM, de Jonge R. Effect of methotrexate use and erythrocyte methotrexate polyglutamate on glycosylated hemoglobin in rheumatoid arthritis. Arthritis Rheumatol. 2014;66:2026-2036. doi: 10.1002/art.38652 182. Ridker PM, Everett BM, Pradhan A, MacFadyen JG, Solomon DH, Zaharris E, Mam V, Hasan A, Rosenberg Y, Iturriaga E, et al.; CIRT Investigators. Low-dose methotrexate for the prevention of atherosclerotic events. N Engl J Med. 2019;380:752-762. doi: 10.1056/NEJMoa1809798 183. · DOI
  132. Larsen CM, Faulenbach M, Vaag A, Vølund A, Ehses JA, Seifert B, Mandrup-Poulsen T, Donath MY. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med. 2007;356:1517-1526. doi: 10.1056/NEJMoa065213 185. · DOI
  133. Cavelti-Weder C, Babians-Brunner A, Keller C, Stahel MA, Kurz-Levin M, Zayed H, Solinger AM, Mandrup-Poulsen T, Dinarello CA, Donath MY. Effects of gevokizumab on glycemia and inflammatory markers in type 2 diabetes. Diabetes Care. 2012;35:1654-1662. doi: 10.2337/dc11-2219 186. · DOI
  134. Everett BM, Donath MY, Pradhan AD, Thuren T, Pais P, Nicolau JC, Glynn RJ, Libby P, Ridker PM. Anti-inflammatory therapy with canakinumab for the prevention and management of diabetes. J Am Coll Cardiol. 2018;71:2392-2401. doi: 10.1016/j.jacc.2018.03.002 187. · DOI
  135. Kataria Y, Ellervik C, Mandrup-Poulsen T. Treatment of type 2 diabe- tes by targeting interleukin-1: a meta-analysis of 2921 patients. Semin Immunopathol. 2019;41:413-425. doi: 10.1007/s00281-019-00743-6 188. · DOI
  136. Huh JH, Kim HM, Lee ES, Kwon MH, Lee BR, Ko HJ, Chung CH. Dual CCR2/5 Antagonist attenuates obesity-induced insulin resistance by reg- ulating macrophage recruitment and M1/M2 status. Obesity (Silver Spring). 2018;26:378-386. doi: 10.1002/oby.22103 189. · DOI
  137. Di Prospero NA, Artis E, Andrade-Gordon P, Johnson DL, Vaccaro N, Xi L, Rothenberg P. CCR2 antagonism in patients with type 2 diabetes mellitus: a randomized, placebo-controlled study. Diabetes Obes Metab. 2014;16:1055-1064. doi: 10.1111/dom.12309 190. · DOI
  138. Tuttle KR, Brosius FC III, Adler SG, Kretzler M, Mehta RL, Tumlin JA, Tanaka Y, Haneda M, Liu J, Silk ME, et al. JAK1/JAK2 inhibition by bar- icitinib in diabetic kidney disease: results from a Phase 2 randomized controlled clinical trial. Nephrol Dial Transplant. 2018;33:1950-1959. doi: 10.1093/ndt/gfx377 193. · DOI
  139. Stekovic S, Hofer SJ, Tripolt N, Aon MA, Royer P, Pein L, Stadler JT, Pendl T, Prietl B, Url J, et al. Alternate day fasting improves physiological and molecular markers of aging in healthy, non-obese humans. Cell Metab. 2019;30:462-476.e6. doi: 10.1016/j.cmet.2019.07.016 195. · DOI

Cited by

Sorted by citations

Authors
Wu, H., & Ballantyne, C. M.
Affiliations
Baylor College of Medicine (US)
ORCID
Ballantyne, Christie M.
Venue
Circulation Research
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2020-05-22
Volume
126
Issue
11
Pages
1549-1564
ISSN
  • 0009-7330 (ISSN-L)
  • 1524-4571
DOI
10.1161/circresaha.119.315896
PMC
PMC7250139
OpenAlex
W3027726841
Cited by
1,059
References
38
Citations by year
2026: 170 · 2025: 225 · 2024: 206 · 2023: 213 · 2022: 147 · 2021: 80 · 2020: 15 · 2019: 1 · 2012: 1
FWCI
16.78
Type
journal article
Language
en
Open access
Locations
  • Circulation Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • American Heart Association (16GRNT30410012)
  • National Heart, Lung, and Blood Institute (R01HL134320, R01HL098839)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK121348)
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
obesity, metabolic inflammation, insulin resistance, type 2 diabetes, adipose tissue inflammation, immune cell polarization, atherosclerotic cardiovascular disease, anti-inflammatory therapy, skeletal muscle, liver, intestine, pancreatic islets, brain
MeSH terms
Animals, Humans, Insulin Resistance, Obesity, Signal Transduction, Cytokines

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