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Microenvironment of Immune Cells Within the Visceral Adipose Tissue Sensu Lato vs. Epicardial Adipose Tissue: What Do We Know?

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Abstract

The chronic low-grade inflammation of the visceral adipose tissue is now fully established as one of the main contributors to metabolic disorders such as insulin resistance, subsequently leading to metabolic syndrome and other associated cardiometabolic pathologies. The orchestration of immune response and the “ratio of responsibility” of different immune cell populations have been studied extensively over the last few years within the visceral adipose tissue in general sense (sensu lato). However, it is essential to clearly distinguish different types of visceral fat distribution. Visceral adipose tissue is not only the classical omental or epididymal depot, but includes also specific type of fat in the close vicinity to the myocardium—the epicardial adipose tissue. Disruption of this type of fat during obesity was found to have a unique and direct influence over the cardiovascular disease development. Therefore, epicardial adipose tissue and other types of visceral adipose tissue depots should be studied separately. The purpose of this review is to explore the present knowledge about the morphology and dynamics of individual populations of immune cells within the visceral adipose tissue sensu lato in comparison to the knowledge regarding the epicardial adipose tissue specifically.

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References

  1. Kershaw, E.E., and J.S. Flier. 2004. Adipose tissue as an endocrine organ. The Journal of Clinical Endocrinology & Metabolism 89 (6): 2548–2556.

    Article  CAS  Google Scholar 

  2. Maury, E., and S.M. Brichard. 2010. Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome. Molecular and Cellular Endocrinology 314 (1): 1–16.

    Article  PubMed  CAS  Google Scholar 

  3. Berg, A.H., and P.E. Scherer. 2005. Adipose tissue, inflammation. and cardiovascular disease. Circulation Research 96 (9): 939–949.

    PubMed  CAS  Google Scholar 

  4. Könner, A.C., and J.C. Brüning. 2011. Toll-like receptors: linking inflammation to metabolism. Trends in Endocrinology & Metabolism 22 (1): 16–23.

    Article  CAS  Google Scholar 

  5. Ouchi, N., J.L. Parker, J.J. Lugus, and K. Walsh. 2011. Adipokines in inflammation and metabolic disease. Nature Reviews Immunology 11 (2): 85–97.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Lin, Y.W., and L.N. Wei. 2017. Innate immunity orchestrates adipose tissue homeostasis. Hormone Molecular Biology and Clinical Investigation 31 (1).

  7. Mathis, D., and S.E. Shoelson. 2011. Immunometabolism: an emerging frontier. Nature Reviews Immunology 11 (2): 81.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Aravindhan, V., and H. Madhumitha. 2016. Metainflammation in Diabetic Coronary Artery Disease: Emerging Role of Innate and Adaptive Immune Responses. Journal of Diabetes Research 2016: 1–10.

    Article  CAS  Google Scholar 

  9. Dahiya, R., S. Shultz, J. Cardinal, N. Byrne, A. Hills, K. Gibbons, et al. 2015. Resistance training improves metainflammation and body composition in obese adolescents. International Journal of Pediatric Endocrinology 2015 (Suppl 1): O40.

    Article  PubMed Central  Google Scholar 

  10. Wang, W., and P. Seale. 2016. Control of brown and beige fat development. Nature Reviews Molecular Cell Biology 17 (11): 691–702.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Harms, M., and P. Seale. 2013. Brown and beige fat: development, function and therapeutic potential. Nature Medicine 19 (10): 1252–1263.

    Article  PubMed  CAS  Google Scholar 

  12. Porter, S.A., J.M. Massaro, U. Hoffmann, R.S. Vasan, C.J. O’Donnel, and C.S. Fox. 2009. Abdominal subcutaneous adipose tissue: a protective fat depot? Diabetes Care 32 (6): 1068–1075.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Booth, A., A. Magnuson, and M. Foster. 2014. Detrimental and protective fat: body fat distribution and its relation to metabolic disease. Hormone Molecular Biology and Clinical Investigation 17 (1): 13–27.

    Article  PubMed  CAS  Google Scholar 

  14. Iacobellis, G. 2009. Epicardial and pericardial fat: close. but very different. Obesity (Silver Spring) 17 (4): 625.

    Article  Google Scholar 

  15. Iacobellis, G., D. Corradi, and A.M. Sharma. 2005. Epicardial adipose tissue: anatomic biomolecular and clinical relationships with the heart. Nature Clinical Practice Cardiovascular Medicine 2 (10): 536–543.

    Article  PubMed  Google Scholar 

  16. Sacks, H.S., J.N. Fain, B. Holman, P. Cheema, A. Chary, F. Parks, et al. 2009. Uncoupling protein-1 and related messenger ribonucleic acids in human epicardial and other adipose tissues: epicardial fat functioning as brown fat. The Journal of Clinical Endocrinology & Metabolism 94 (9): 3611–3615.

    Article  CAS  Google Scholar 

  17. Marchington, J.M., C.A. Mattacks, and C.M. Pond. 1989. Adipose tissue in the mammalian heart and pericardium: structure. foetal development and biochemical properties. Comparative Biochemistry and Physiology Part B: Comparative Biochemistry 94 (2): 225–232.

    Article  CAS  Google Scholar 

  18. Matloch, Z., T. Kotulák, and M. Haluzík. 2016. The role of epicardial adipose tissue in heart disease. Physiological Research 65 (1): 23–32.

    PubMed  CAS  Google Scholar 

  19. Ouwens, D.M., H. Sell, S. Greulich, and J. Eckel. 2010. The role of epicardial and perivascular adipose tissue in the pathophysiology of cardiovascular disease. Journal of Cellular and Molecular Medicine 14 (9): 2223–2234.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Silaghi, A.C., R. Pais, A. Valea, A.I. Mironiuc, and H. Silaghi. 2011. Epicardial adipose tissue and relationship with coronary artery disease. Central European Journal of Medicine 6 (3): 251–262.

    Google Scholar 

  21. Gaborit, B., I. Abdesselam, and A. Dutour. 2013. Epicardial fat: more than just an "epi" phenomenon? Hormone and Metabolic Research 45 (13): 991–1001.

    Article  PubMed  CAS  Google Scholar 

  22. Nagy, E., A.L. Jermendy, B. Merkely, and P. Maurovich-Horvat. 2017. Clinical importance of epicardial adipose tissue. Archives of Medical Science 13 (4): 864–874.

    Article  PubMed  Google Scholar 

  23. Iacobellis, G. 2014. Epicardial adipose tissue in endocrine and metabolic diseases. Endocrine 46 (1): 8–15.

    Article  PubMed  CAS  Google Scholar 

  24. Akoumianakis, I., and C. Antoniades. 2017. The interplay between adipose tissue and the cardiovascular system: is fat always bad? Cardiovascular Research 113 (9): 999–1008.

    Article  PubMed  Google Scholar 

  25. Antonopoulos, A.S., and C. Antoniades. 2017. The role of epicardial adipose tissue in cardiac biology: classic concepts and emerging roles. The Journal of Physiology 595 (12): 3907–3917.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Viviano, A., X. Yin, A. Zampetaki, M. Fava, M. Gallagher, M. Mayr, et al. 2017. Proteomics of the epicardial fat secretome and its role in post-operative atrial fibrillation. Europace in press.

  27. Leggio, M., P. Severi, S. D’Emidio, and A. Mazza. 2017. Epicardial adipose tissue and atrial fibrillation: The other side of the coin. The Anatolian Journal of Cardiology 17 (5): 415–416.

    Article  PubMed  Google Scholar 

  28. Cakmak, H.A., B. Dincgez Cakmak, C. Abide Yayla, E. Inci Coskun, M. Erturk, and I. Keles. 2017. Assessment of relationships between novel inflammatory markers and presence and severity of preeclampsia: Epicardial fat thickness, pentraxin-3, and neutrophil-to-lymphocyte ratio. Hypertension in Pregnancy 36 (3): 233–239.

    Article  PubMed  CAS  Google Scholar 

  29. Talman, A.H., P.J. Psaltis, J.D. Cameron, I.T. Meredith, S.K. Seneviratne, and D.T. Wong. 2014. Epicardial adipose tissue: far more than a fat depot. Cardiovascular Diagnosis & Therapy 4 (6): 416–429.

    Google Scholar 

  30. Bouchi, R., M. Terashima, Y. Sasahara, M. Asakawa, T. Fukuda, T. Takeuchi, et al. 2017. Luseogliflozin reduces epicardial fat accumulation in patients with type 2 diabetes: a pilot study. Cardiovascular Diabetology 16 (1): 32.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Pawlina, W. 2016. Cardiovascular System. In Histology. A Text and Atlas with Correlated Cell and Molecular Biology, 7th ed., 404-441. Philadelphia: Wolters Kluwer Health.

  32. Iacobellis, G., F. Assael, M.C. Ribaudo, A. Zappaterreno, G. Alessi, U. Di Mario, et al. 2003. Epicardial fat from echocardiography: a new method for visceral adipose tissue prediction. Obesity Research 11 (2): 304–310.

    Article  PubMed  Google Scholar 

  33. Meenakshi, K., M. Rajendran, S. Srikumar, and S. Chidambaram. 2016. Epicardial fat thickness: A surrogate marker of coronary artery disease – Assessment by echocardiography. Indian Heart Journal 68 (3): 336–341.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Tachibana, M., T. Miyoshi, K. Osawa, N. Toh, H. Oe, K. Nakamura, et al. 2016. Measurement of epicardial fat thickness by transthoracic echocardiography for predicting high-risk coronary artery plaques. Heart and Vessels 31 (11): 1758–1766.

    Article  PubMed  Google Scholar 

  35. Fatma, E., K. Bunyamin, S. Savas, U. Mehmet, Y. Selma, B. Ismail, et al. 2015. Epicardial fat thickness in patients with rheumatoid arthritis. African Health Sciences 15 (2): 489–495.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Aydogdu, A., E.Y. Karakas, E. Erkus, İ.H. Altıparmak, E. Savık, T. Ulas, et al. 2017. Epicardial fat thickness and oxidative stress parameters in patients with subclinical hypothyroidism. Archives of Medical Science 13 (2): 383–389.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Opincariu, D., A. Mester, M. Dobra, et al. 2016. Prognostic Value of Epicardial Fat Thickness as a Biomarker of Increased Inflammatory Status in Patients with Type 2 Diabetes Mellitus and Acute Myocardial Infarction. Journal of Cardiovascular Emergencies 2 (1): 11–18.

    Article  Google Scholar 

  38. Spearman, J.V., M. Renker, U.J. Schoepf, A.W. Krazinski, T.L. Herbert, C.N. De Cecco, et al. 2015. Prognostic value of epicardial fat volume measurements by computed tomography: a systematic review of the literature. European Radiology 25 (11): 3372–3381.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Cohen, P., and B.M. Spiegelman. 2016. Cell biology of fat storage. Molecular Biology of the Cell 27 (16): 2523–2527.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Han, S., H.M. Sun, K.C. Hwang, and S.W. Kim. 2015. Adipose-Derived Stromal Vascular Fraction Cells: Update on Clinical Utility and Efficacy. Critical Reviews in Eukaryotic Gene Expression 25 (2): 145–152.

    Article  PubMed  Google Scholar 

  41. Huh, J.Y., Y.J. Park, M. Ham, and J.B. Kim. 2014. Crosstalk between adipocytes and immune cells in adipose tissue inflammation and metabolic dysregulation in obesity. Molecules and Cells 37 (5): 365–371.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Hill, A.A., W. Reid Bolus, and A.H. Hasty. 2014. A decade of progress in adipose tissue macrophage biology. Immunological Reviews 262 (1): 134–152.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Panee, J. 2012. Monocyte Chemoattractant Protein 1 (MCP-1) in Obesity and Diabetes. Cytokine 60 (1): 1–12.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Kim, D., J. Kim, J.H. Yoon, J. Ghim, K. Yea, P. Song, et al. 2014. CXCL12 secreted from adipose tissue recruits macrophages and induces insulin resistance in mice. Diabetologia 57 (7): 1456–1465.

    Article  PubMed  CAS  Google Scholar 

  45. Nomiyama, T., D. Perez-Tilve, D. Ogawa, F. Gizard, Y. Zhao, E.B. Heywood, et al. 2007. Osteopontin mediates obesity-induced adipose tissue macrophage infiltration and insulin resistance in mice. The Journal of Clinical Investigation 117 (10): 2877–2888.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Patsouris, D., J.G. Neels, W. Fan, P. Li, M.T.A. Nguyen, and J.M. Olefsky. 2009. Glucocorticoids and thiazolidinediones interfere with adipocyte-mediated macrophage chemotaxis and recruitment. The Journal of Biological Chemistry 284 (45): 31223–31235.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Saberi, M., N.B. Woods, C. de Luca, S. Schenk, J.C. Lu, G. Bandyopadhyay, et al. 2009. Hematopoietic cell-specific deletion of toll-like receptor 4 ameliorates hepatic and adipose tissue insulin resistance in high-fat-fed mice. Cell Metabolism 10 (5): 419–429.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Hosogai, N., A. Fukuhara, K. Oshima, Y. Miyata, S. Tanaka, K. Segawa, et al. 2007. Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation. Diabetes 56 (4): 901–911.

    Article  PubMed  CAS  Google Scholar 

  49. Gruen, M.L., M. Hao, D.W. Piston, and A.H. Hasty. 2007. Leptin requires canonical migratory signaling pathways for induction of monocyte and macrophage chemotaxis. American Journal of Physiology-CellPhysiology 293 (5): C1481–C1488.

    Article  CAS  Google Scholar 

  50. Kosteli, A., E. Sugaru, G. Haemmerle, J.F. Martin, J. Lei, R. Zechner, et al. 2010. Weight loss and lipolysis promote a dynamic immune response in murine adipose tissue. The Journal of Clinical Investigation 120 (10): 3466–3479.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Sasaki, Y., M. Ohta, D. Desai, J.L. Figueiredo, M.C. Whelan, T. Sugano, et al. 2015. Angiopoietin Like Protein 2 (ANGPTL2) Promotes Adipose Tissue Macrophage and T lymphocyte Accumulation and Leads to Insulin Resistance. PLoS ONE 10 (7): e0131176.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Har, D., M. Carey, and M. Hawkins. 2013. Coordinated Regulation of Adipose Tissue Macrophages by Cellular and Nutritional Signals. Journal of Investigative Medicine : The Official Publication of the American Federation for Clinical Research 61 (6): 937–941.

    Article  CAS  Google Scholar 

  53. Morris, D.L., K.W. Cho, J.L. DelProposto, K.E. Oatmen, L.M. Geletka, G. Martinez-Santibanez, et al. 2013. Adipose tissue macrophages function as antigen-presenting cells and regulate adipose tissue CD4+ T cells in mice. Diabetes 62 (8): 2762–2772.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Li, P., M. Lu, M.T. Nguyen, E.J. Bae, J. Chapman, D. Feng, et al. 2010. Functional heterogeneity of CD11c-positive adipose tissue macrophages in diet-induced obese mice. Journal of Biological Chemistry 285 (20): 15333–15345.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  55. Lumeng, C.N., J.B. DelProposto, D.J. Westcott, and A.R. Saltiel. 2008. Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes. Diabetes 57 (12): 3239–3246.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Altintas, M.M., A. Azad, B. Nayer, G. Contreras, J. Zaias, C. Faul, et al. 2011. Mast cells, macrophages, and crown-like structures distinguish subcutaneous from visceral fat in mice. Journal of Lipid Research 52 (3): 480–488.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Cancello, R., J. Tordjman, C. Poitou, G. Guihem, J.L. Bouillot, D. Hugol, et al. 2006. Increased infiltration of macrophages in omental adipose tissue is associated with marked hepatic lesions in morbid human obesity. Diabetes 55 (6): 1554–1561.

    Article  PubMed  CAS  Google Scholar 

  58. Aron-Wisnewsky, J., J. Tordjman, C. Poitou, F. Darakhshan, D. Hugol, A. Basdevant, et al. 2009. Human adipose tissue macrophages: m1 and m2 cell surface markers in subcutaneous and omental depots and after weight loss. The Journal of Clinical Endocrinology & Metabolism 94 (11): 4619–4623.

    Article  CAS  Google Scholar 

  59. Wentworth, J.M., G. Naselli, W.A. Brown, L. Doyle, B. Phipson, G.K. Smyth, et al. 2010. Pro-inflammatory CD11c+CD206+ adipose tissue macrophages are associated with insulin resistance in human obesity. Diabetes 59 (7): 1648–1656.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Morris, D.L., K. Singer, and C.N. Lumeng. 2011. Adipose tissue macrophages: phenotypic plasticity and diversity in lean and obese states. Current Opinion in Clinical Nutrition and Metabolic Care 14 (4): 341–346.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Boutens, L., and R. Stienstra. 2016. Adipose tissue macrophages: going off track during obesity. Diabetologia 59 (5): 879–894.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Thomas, D., and C. Apovian. 2017. Macrophage functions in lean and obese adipose tissue. Metabolism 72: 120–143.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Yong, S.B., Y. Song, and Y.H. Kim. 2017. Visceral adipose tissue macrophage-targeted TACE silencing to treat obesity-induced type 2 diabetes. Biomaterials 148: 81–89.

    Article  PubMed  CAS  Google Scholar 

  64. Hirata, Y., M. Tabata, H. Kurobe, T. Motoki, M. Akaike, C. Nishio, et al. 2011. Coronary atherosclerosis is associated with macrophage polarization in epicardial adipose tissue. Journal of American College of Cardiology 58 (3): 248–255.

    Article  CAS  Google Scholar 

  65. Vianello, E., E. Dozio, F. Arnaboldi, M.G. Marazzi, C. Martinelli, J. Lamont, et al. 2016. Epicardial adipocyte hypertrophy: Association with M1-polarization and toll-like receptor pathways in coronary artery disease patients. Nutrition, Metabolism and Cardiovascular Diseases 26 (3): 246–253.

    Article  PubMed  CAS  Google Scholar 

  66. Kitagawa, T., H. Yamamoto, K. Sentani, S. Takahashi, H. Tsushima, A. Senoo, et al. 2015. The relationship between inflammation and neoangiogenesis of epicardial adipose tissue and coronary atherosclerosis based on computed tomography analysis. Atherosclerosis 243 (1): 293–299.

    Article  PubMed  CAS  Google Scholar 

  67. Gurses, K.M., F. Ozmen, D. Kocyigit, N. Yersal, E. Bilgic, E. Kaya, et al. 2017. Netrin-1 is associated with macrophage infiltration and polarization in human epicardial adipose tissue in coronary artery disease. Journal of Cardiology 69 (6): 851–858.

    Article  PubMed  Google Scholar 

  68. Cools, N., P. Ponsaerts, V.F. Van Tendeloo, and Z.N. Berneman. 2007. Balancing between immunity and tolerance: an interplay between dendritic cells, regulatory T cells, and effector T cells. Journal of Leukocyte Biology 82 (6): 1365–1374.

    Article  PubMed  CAS  Google Scholar 

  69. Chung, C.Y.J., D. Ysebaert, Z.N. Berneman, and N. Cools. 2013. Dendritic Cells: cellular mediators for immunological tolerance. Clinical and Developmental Immunology 2013: 972865.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Pamir, N., N.C. Liu, A. Irwin, L. Becker, Y. Peng, G.E. Ronsein, et al. 2015. Granulocyte/Macrophage Colony-stimulating Factor-dependent Dendritic Cells Restrain Lean Adipose Tissue Expansion. The Journal of Biological Chemistry 290 (23): 14656–14667.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Stefanovic-Racic, M., X. Yang, M.S. Turner, B.S. Mantell, D.B. Stolz, T.L. Sumpter, et al. 2012. Dendritic cells promote macrophage infiltration and comprise a substantial proportion of obesity-associated increases in CD11c+ cells in adipose tissue and liver. Diabetes 61 (9): 2330–2339.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Chen, Y., J. Tian, X. Tian, X. Tang, K. Rui, J. Tong, et al. 2014. Adipose tissue dendritic cells enhances inflammation by prompting the generation of Th17 cells. PLoS ONE 9 (3): e92450.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Bertola, A., T. Ciucci, D. Rousseau, V. Bourlier, C. Duffaut, S. Bonnafous, et al. 2012. Identification of adipose tissue dendritic cells correlated with obesity-associated insulin-resistance and inducing Th17 responses in mice and patients. Diabetes 2012 61 (9): 2238–2247.

    CAS  Google Scholar 

  74. Cho, K.W., B.F. Zamarron, L.A. Muir, K. Singer, C.E. Porsche, J.B. DelProposto, et al. 2016. Adipose Tissue Dendritic Cells Are Independent Contributors to Obesity-Induced Inflammation and Insulin Resistance. The Journal of Immunology 197 (9): 3650–3661.

    Article  PubMed  CAS  Google Scholar 

  75. Ghosh, A.R., R. Bhattacharya, S. Bhattacharya, T. Nargis, O. Rahaman, P. Duttagupta, et al. 2016. Adipose Recruitment and Activation of Plasmacytoid Dendritic Cells Fuel Metaflammation. Diabetes 65 (11): 3440–3452.

    Article  PubMed  CAS  Google Scholar 

  76. Shi, M.A., and G.P. Shi. 2012. Different roles of mast cells in obesity and diabetes: lessons from experimental animals and humans. Frontiers in Immunology 3: 7.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Ishijima, Y., S. Ohmori, and K. Ohneda. 2013. Mast cell deficiency results in the accumulation of preadipocytes in adipose tissue in both obese and non-obese mice. FEBS Open Bio 4: 18–24.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Divoux, A., S. Moutel, C. Poitou, D. Lacasa, N. Veyrie, A. Aissat, et al. 2012. Mast cells in human adipose tissue: link with morbid obesity, inflammatory status, and diabetes. The Journal of Clinical Endocrinology & Metabolism 97 (9): E1677–E1685.

    Article  CAS  Google Scholar 

  79. Liu, J., A. Divoux, J. Sun, J. Zhang, K. Clément, J.N. Glickman, et al. 2009. Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice. Nature Medicine 15 (8): 940–945.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Gutierrez, D.A., S. Muralidhar, T.B. Feyerabend, S. Herzig, and H.R. Rodewald. 2015. Hematopoietic Kit Deficiency, rather than Lack of Mast Cells, Protects Mice from Obesity and Insulin Resistance. Cell Metabolism 21 (5): 678–691.

    Article  PubMed  CAS  Google Scholar 

  81. Chmelař, J., A. Chatzigeorgiou, K.-J. Chung, M. Prucnal, D. Voehringer, A. Roers, et al. 2016. No Role for Mast Cells in Obesity-Related Metabolic Dysregulation. Frontiers in Immunology 7: 524.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Einwallner, E., F.W. Kiefer, G. Di Caro, M. Orthofer, N. Witzeneder, G. Hörmann, et al. 2016. Mast cells are not associated with systemic insulin resistance. European Journal of Clinical Investigation 46 (11): 911–919.

    Article  PubMed  CAS  Google Scholar 

  83. Bais, S., R. Kumari, Y. Prashar, and N.S. Gill. 2017. Review of various molecular targets on mast cells and its relation to obesity: A future perspective. Diabetes & Metabolic Syndrome: Clinical Research & Reviews 11 (Suppl 2): S1001–S1007.

    Article  Google Scholar 

  84. Laine, P., M. Kaartinen, A. Penttilä, P. Panula, T. Paavonen, and P.T. Kovanen. 1999. Association between myocardial infarction and the mast cells in the adventitia of the infarct-related coronary artery. Circulation 99 (3): 361–369.

    Article  PubMed  CAS  Google Scholar 

  85. Laine, P., A. Naukkarinen, L. Heikkilä, A. Penttilä, and P.T. Kovanen. 2000. Adventitial mast cells connect with sensory nerve fibers in atherosclerotic coronary arteries. Circulation 101 (14): 1665–1669.

    Article  PubMed  CAS  Google Scholar 

  86. Elgazar-Carmon, V., A. Rudich, N. Hadad, and R. Levy. 2008. Neutrophils transiently infiltrate intra–abdominal fat early in the course of high–fat feeding. Journal of Lipid Research 49 (9): 1894–1903.

    Article  PubMed  CAS  Google Scholar 

  87. Hadad, N., O. Burgazliev, V. Elgazar-Carmon, Y. Solomonov, S. Wueest, F. Item, et al. 2013. Induction of Cytosolic Phospholipase A2α Is Required for Adipose Neutrophil Infiltration and Hepatic Insulin Resistance Early in the Course of High-Fat Feeding. Diabetes 62 (9): 3053–3063.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Bijnen, M., T. Josefs, I. Cuijpers, C.J. Maalsen, J. van de Gaar, M. Vroomen, et al. 2017. Adipose tissue macrophages induce hepatic neutrophil recruitment and macrophage accumulation in mice. Gut 2017 (in press).

  89. Talukdar, S., D.Y. Oh, G. Bandyopadhyay, D. Li, J. Xu, J. McNelis, et al. 2012. Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Nature Medicine 18 (9): 1407–1412.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. Mansuy-Aubert, V., Q.L. Zhou, X. Xie, Z. Gong, J.Y. Huang, A.R. Khan, et al. 2013. Imbalance between neutrophil elastase and its inhibitor α1-antitrypsin in obesity alters insulin sensitivity, inflammation, and energy expenditure. Cell Metabolism 17 (4): 534–548.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Wang, Q., Z. Xie, W. Zhang, J. Zhou, Y. Wu, M. Zhang, et al. 2014. Myeloperoxidase Deletion Prevents High-Fat Diet–Induced Obesity and Insulin Resistance. Diabetes 63 (12): 4172–4185.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Tagzirt, M., D. Corseaux, L. Pasquesoone, F. Mouquet, C. Roma-Lavisse, A. Ung, et al. 2014. Alterations in Neutrophil Production and Function at an Early Stage in the High-Fructose Rat Model of Metabolic Syndrome. American Journal of Hypertension 27 (8): 1096–1104.

    Article  PubMed  CAS  Google Scholar 

  93. Akbas, E.M., L. Demirtas, A. Ozcicek, A. Timuroglu, E.M. Bakirci, H. Hamur, et al. 2014. Association of epicardial adipose tissue, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio with diabetic nephropathy. International Journal of Clinical and Experimental Medicine 7 (7): 1794–1801.

    PubMed  PubMed Central  Google Scholar 

  94. Akdag, S., H. Simsek, M. Sahin, A. Akyol, R. Duz, and N. Babat. 2015. Association of epicardial adipose tissue thickness and inflammation parameters with CHA2DS2-VASASc score in patients with nonvalvular atrial fibrillation. Therapeutics and Clinical Risk Management 11: 1675–1681.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Akbas, E.M., H. Hamur, L. Demirtas, E.M. Bakirci, A. Ozcicek, F. Ozcicek, et al. 2014. Predictors of epicardial adipose tissue in patients with type 2 diabetes mellitus. Diabetology & Metabolic Syndrome 6: 55.

    Article  Google Scholar 

  96. Bakirci, E.M., H. Degirmenci, H. Duman, S. Inci, H. Hamur, M. Buyuklu, et al. 2015. Increased Epicardial Adipose Tissue Thickness is Associated With Angiographic Thrombus Burden in the Patients With Non-ST-Segment Elevation Myocardial Infarction. Clinical and Applied Thrombosis/Hemostasis 21 (7): 612–618.

    Article  CAS  Google Scholar 

  97. Ozcicek, A., F. Ozcicek, G. Yildiz, A. Timuroglu, L. Demirtas, M. Buyuklu, et al. 2017. Neutrophil-to-lymphocyte ratio as a possible indicator of epicardial adipose tissue in patients undergoing hemodialysis. Archives of Medical Science 13 (1): 118–123.

    Article  PubMed  Google Scholar 

  98. Molofsky, A.B., J.C. Nussbaum, H.E. Liang, S.J. Van Dyken, L.E. Cheng, A. Mohapatra, et al. 2013. Innate lymphoid type 2 cells sustain visceral adipose tissue eosinophils and alternatively activated macrophages. The Journal of Experimental Medicine 210 (3): 535–549.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Qiu, Y., K.D. Nguyen, J.I. Odegaard, X. Cui, X. Tian, R.M. Locksley, et al. 2014. Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat. Cell 157 (6): 1292–1308.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  100. Bolus, W.R., D.A. Gutierrez, A.J. Kennedy, E.K. Anderson-Baucum, and A.H. Hasty. 2015. CCR2 deficiency leads to increased eosinophils, alternative macrophage activation, and type 2 cytokine expression in adipose tissue. Journal of Leukocyte Biology 98 (4): 467–477.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  101. Wu, D., A.B. Molofsky, H.E. Liang, R.R. Ricardo-Gonzalez, H.A. Jouihan, J.K. Bando, et al. 2011. Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science 332 (6026): 243–247.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  102. Withers, S.B., R. Forman, S. Meza-Perez, D. Sorobetea, K. Sitnik, T. Hopwood, et al. 2017. Eosinophils are key regulators of perivascular adipose tissue and vascular functionality. Scientific Reports 7: 44571.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  103. O’Sullivan, T.E., M. Rapp, X. Fan, O.E. Weizman, P. Bhardwaj, N.M. Adams, et al. 2016. Adipose-Resident Group 1 Innate Lymphoid Cells Promote Obesity-Associated Insulin Resistance. Immunity 45 (2): 428–441.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  104. Artis, D., and H. Spits. 2015. The biology of innate lymphoid cells. Nature 517 (7534): 293–301.

    Article  PubMed  CAS  Google Scholar 

  105. Boulenouar, S., X. Michelet, D. Duquette, D. Alvarez, A.E. Hogan, C. Dold, et al. 2017. Adipose Type One Innate Lymphoid Cells Regulate Macrophage Homeostasis through Targeted Cytotoxicity. Immunity 46 (2): 273–286.

    Article  PubMed  CAS  Google Scholar 

  106. Newland, S.A., S. Mohanta, M. Clément, S. Taleb, J.A. Walker, M. Nus, et al. 2017. Type-2 innate lymphoid cells control the development of atherosclerosis in mice. Nature Communications 8: 15781.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  107. Hashiguchi, M., Y. Kashiwakura, H. Kojima, A. Kobayashi, Y. Kanno, and T. Kobata. 2015. IL-33 activates eosinophils of visceral adipose tissue both directly and via innate lymphoid cells. European Journal of Immunology 45 (3): 876–885.

    Article  PubMed  CAS  Google Scholar 

  108. Brestoff, J.R., B.S. Kim, S.A. Saenz, R.R. Stine, L.A. Monticelli, G.F. Sonnenberg, et al. 2015. Group 2 innate lymphoid cells promote beiging of white adipose tissue and limit obesity. Nature 519 (7542): 242–246.

    Article  PubMed  CAS  Google Scholar 

  109. Larosa, D.F., and J.S. Orange. 2008. 1. Lymphocytes. Journal of Allergy and Clinical Immunology 121 (2 Suppl): S364–S369.

    Article  PubMed  CAS  Google Scholar 

  110. Zhou, L., M.M. Chong, and D.R. Littman. 2009. Plasticity of CD4+ T cell lineage differentiation. Immunity 30 (5): 646–655.

    Article  PubMed  CAS  Google Scholar 

  111. Oestreich, K.J., and A.S. Weinmann. 2012. Master regulators or lineage-specifying? Changing views on CD4+ T cell transcription factors. Nature Reviews Immunology 12 (11): 799–804.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  112. Mraz, M., and M. Haluzik. 2014. The role of adipose tissue immune cells in obesity and low-grade inflammation. Journal of Endocrinology 222 (3): R113–R127.

    Article  PubMed  CAS  Google Scholar 

  113. Zeyda, M., J. Huber, G. Prager, and T.M. Stulnig. 2011. Inflammation correlates with markers of T-cell subsets including regulatory T cells in adipose tissue from obese patients. Obesity (Silver Spring) 19 (4): 743–748.

    Article  CAS  Google Scholar 

  114. Fabbrini, E., M. Cella, S.A. McCartney, A. Fuchs, N.A. Abumrad, T.A. Pietka, et al. 2013. Association between specific adipose tissue CD4+ T-cell populations and insulin resistance in obese individuals. Gastroenterology 145 (2): 366–374.

    Article  PubMed  CAS  Google Scholar 

  115. Wu, H., S. Ghosh, X.D. Perrard, L. Feng, G.E. Garcia, J.L. Perrard, et al. 2007. T-cell accumulation and regulated on activation, normal T cell expressed and secreted upregulation in adipose tissue in obesity. Circulation 115 (8): 1029–1038.

    Article  PubMed  CAS  Google Scholar 

  116. Feuerer, M., L. Herrero, D. Cipolletta, A. Naaz, J. Wong, A. Nayer, et al. 2009. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nature Medicine 15 (8): 930–939.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  117. Winer, S., Y. Chan, G. Paltser, D. Truong, H. Tsui, J. Bahrami, et al. 2009. Normalization of Obesity-Associated Insulin Resistance through Immunotherapy: CD4+ T Cells Control Glucose Homeostasis. Nature Medicine 15 (8): 921–929.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  118. Kintscher, U., M. Hartge, K. Hess, A. Foryst-Ludwig, M. Clemenz, M. Wabitsch, et al. 2008. T-lymphocyte infiltration in visceral adipose tissue: a primary event in adipose tissue inflammation and the development of obesity-mediated insulin resistance. Arteriosclerosis, Thrombosis, and Vascular Biology 28 (7): 1304–1310.

    Article  PubMed  CAS  Google Scholar 

  119. Duffaut, C., A. Zakaroff-Girard, V. Bourlier, P. Decaunes, M. Maumus, P. Chiotasso, et al. 2009. Interplay between human adipocytes and T lymphocytes in obesity: CCL20 as an adipochemokine and T lymphocytes as lipogenic modulators. Arteriosclerosis, Thrombosis, and Vascular Biology 29 (10): 1608–1614.

    Article  PubMed  CAS  Google Scholar 

  120. Rocha, V.Z., E.J. Folco, G. Sukhova, K. Shimizu, I. Gotsman, A.H. Vernon, et al. 2008. Interferon-gamma, a Th1 cytokine, regulates fat inflammation: a role for adaptive immunity in obesity. Circulation Research 103 (5): 467–476.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  121. Nishimura, S., I. Manabe, M. Nagasaki, K. Eto, H. Yamashita, M. Ohsugi, et al. 2009. CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nature Medicine 15 (8): 914–920.

    Article  PubMed  CAS  Google Scholar 

  122. Wolf, D., F. Jehle, N.A. Michel, E.N. Bukosza, J. Rivera, Y.C. Chen, et al. 2014. Coinhibitory suppression of T cell activation by CD40 protects against obesity and adipose tissue inflammation in mice. Circulation 129 (23): 2414–2425.

    Article  PubMed  CAS  Google Scholar 

  123. Yi, Z., and G.A. Bishop. 2014. Regulatory role of CD40 in obesity-induced insulin resistance. Adipocyte 4 (1): 65–69.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  124. McLaughlin, T., L.F. Liu, C. Lamendola, L. Shen, J. Morton, H. Rivas, et al. 2014. T-cell profile in adipose tissue is associated with insulin resistance and systemic inflammation in humans. Arteriosclerosis, Thrombosis, and Vascular Biology 34 (12): 2637–2643.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  125. Shin, J.H., D.W. Shin, and M. Noh. 2009. Interleukin-17A inhibits adipocyte differentiation in human mesenchymal stem cells and regulates pro-inflammatory responses in adipocytes. Biochemical Pharmacology 77 (12): 1835–1844.

    Article  PubMed  CAS  Google Scholar 

  126. Deiuliis, J., Z. Shah, N. Shah, B. Needleman, D. Mikami, V. Narula, et al. 2011. Visceral adipose inflammation in obesity is associated with critical alterations in tregulatory cell numbers. PLoS ONE 6 (1): e16376.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  127. Pettersson, U.S., T.B. Waldén, P.O. Carlsson, L. Jansson, and M. Phillipson. 2012. Female mice are protected against high-fat diet induced metabolic syndrome and increase the regulatory T cell population in adipose tissue. PLoS ONE 7 (9): e46057.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  128. Hirata, Y., H. Kurobe, M. Akaike, F. Chikugo, T. Hori, Y. Bando, et al. 2011. Enhanced inflammation in epicardial fat in patients with coronary artery disease. International Heart Journal 52 (3): 139–142.

    Article  PubMed  CAS  Google Scholar 

  129. Miksztowicz, V., C. Morales, M. Barchuk, G. López, R. Póveda, R. Gelpi, et al. 2017. Metalloproteinase 2 and 9 Activity Increase in Epicardial Adipose Tissue of Patients with Coronary Artery Disease. Current Vascular Pharmacology 15 (2): 135–143.

    Article  PubMed  CAS  Google Scholar 

  130. Winer, D.A., S. Winer, L. Shen, P.P. Wadia, J. Yantha, G. Paltser, et al. 2011. B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nature Medicine 17 (5): 610–617.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  131. Shen, L., M.H. Chng, M.N. Alonso, R. Yuan, D.A. Winer, and E.G. Engleman. 2015. B-1a lymphocytes attenuate insulin resistance. Diabetes 64 (2): 593–603.

    Article  PubMed  CAS  Google Scholar 

  132. Harmon, D.B., P. Srikakulapu, J.L. Kaplan, S.N. Oldham, C. McSkimming, J.C. Garmey, et al. 2016. Protective Role for B-1b B Cells and IgM in Obesity-Associated Inflammation, Glucose Intolerance. and Insulin Resistance. Arteriosclerosis, Thrombosis, and Vascular Biology 36 (4): 682–691.

    Article  PubMed  CAS  Google Scholar 

  133. Nishimura, S., I. Manabe, S. Takaki, M. Nagasaki, M. Otsu, H. Yamashita, et al. 2013. Adipose Natural Regulatory B Cells Negatively Control Adipose Tissue Inflammation. Cell Metabolism 18 (5): 759–766.

    Article  CAS  PubMed  Google Scholar 

  134. DeFuria, J., A.C. Belkina, M. Jagannathan-Bogdan, J. Snyder-Cappione, J.D. Carr, Y.R. Nersesova, et al. 2013. B cells promote inflammation in obesity and type 2 diabetes through regulation of T-cell function and an inflammatory cytokine profile. Proceedings of the National Academy of Sciences of the United States of America 110 (13): 5133–5138.

    Article  PubMed  PubMed Central  Google Scholar 

  135. Winer, D.A., S. Winer, L. Shen, M.H. Chng, and E.G. Engleman. 2012. B lymphocytes as emerging mediators of insulin resistance. International Journal of Obesity Supplements 2 (Suppl 1): S4–S7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  136. Frasca, D., A. Diaz, M. Romero, T. Vazquez, and B.B. Blomberg. 2017. Obesity induces pro-inflammatory B cells and impairs B cell function in old mice. Mechanisms of Ageing and Development 162: 91–99.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  137. Srikakulapu, P., A. Upadhye, S.M. Rosenfeld, M.A. Marshall, C. McSkimming, A.W. Hickman, et al. 2017. Perivascular Adipose Tissue Harbors Atheroprotective IgM-Producing B Cells. Frontiers in Physiology 8: 719.

    Article  PubMed  PubMed Central  Google Scholar 

  138. Mazurek, T., L. Zhang, A. Zalewski, J.D. Mannion, J.T. Diehl, H. Arafat, et al. 2003. Human epicardial adipose tissue is a source of inflammatory mediators. Circulation 108 (20): 2460–2466.

    Article  PubMed  Google Scholar 

  139. Martyniak, K., and M.M. Masternak. 2017. Changes in adipose tissue cellular composition during obesity and aging as a cause of metabolic dysregulation. Experimental Gerontology 94: 59–63.

    Article  PubMed  CAS  Google Scholar 

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Funding

This work was supported by Grant of The Slovak Research and Development Agency No. APVV-0434-12.

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Klein, M., Varga, I. Microenvironment of Immune Cells Within the Visceral Adipose Tissue Sensu Lato vs. Epicardial Adipose Tissue: What Do We Know?. Inflammation 41, 1142–1156 (2018). https://doi.org/10.1007/s10753-018-0798-3

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