Adipoparacrinology: An emerging field in biomedical research

Beyaz adipoz doku (BAD) adipositler ve fibroblastlardan, endotelyal ve immün hücreler, sinir lifleri ve kök hücrelerini içeren stromavasküler hücrelerden oluşan dinamik multisellüler bir topluluktur. İnsanlarda BAD, iki büyük depoya (subkutan ve visseral) ve kalp, kan damarları, majör lenf nodları, prostat bezi, overler ve meme bezleri ile ilişkili birçok küçük depoya bölünmüş yanıt veren ve sekretuar (endokrin ve parakrin) bir dokudur. Bu kısa derleme adipoparakrinoloji adında yeni bir araştırma alanı kurmada adipoz dokunun parakrin aktivitesi hakkındaki kanıtları kavramsallaştırmaktadır. Burada şunlara odaklanmaktayız (i) aterogenezde epikardiyal ve periadventisyal adipoz doku, (ii) meme kanserinde meme bezi ile ilişkili adipoz doku ve (iii) prostat kanserinde periprostatik adipoz doku. Diğer örnekler şunları içermektedir: (i) Crohn hastalığında mezenterik adipoz doku, (ii) Crohn hastalığında lenf nodu ile ilişkili (perinodal) adipoz doku ve HIV ile ilişkili adipoz yeniden dağılım sendromu, (iii) diz osteoartritinde infrapatellar yağ yastıkçığı (Hoffa yağ yastıkçığı), (iv) tiroit ile ilişkili (Graves) oftalmopatide orbital adipoz doku ve (v) beyin bozukluklarında parasellar bölge ile ilşikili adipoz doku. Adipoparakrinolojinin tedavi yönü de ayrıca tartışılmaktadır.

Adipoparakrinoloji: Biyomedikal araştırmalarda gelişmekte olan bir alan

White adipose tissue (WAT) is a dynamic multicellular assembly composed of adipocytes and stromovascular cells, including fibroblasts, endothelial and immune cells, nerve fibers, and stem cells. In humans, WAT is a responsive and secretory (endocrine and paracrine) tissue partitioned into two large depots (subcutaneous and visceral) and many small depots associated with the heart, blood vessels, major lymph nodes, prostate gland, ovaries and mammary glands. This short review conceptualizes evidence for the paracrine activity of adipose tissue in founding a new research field, designated adipoparacrinology. Here we focus on (i) epicardial and periadventitial adipose tissue in atherogenesis, (ii) mammary gland-associated adipose tissue in breast cancer, and (iii) periprostatic adipose tissue in prostate cancer. Other examples include: (i) mesenteric adipose tissue in Crohn's disease, (ii) lymph node-associated (perinodal) adipose tissue in Crohn's disease and HIV-associated adipose redistribution syndrome, (iii) infrapatellar fat pad (Hoffa's fat pad) in knee osteoarthritis, (iv) orbital adipose tissue in thyroid-associated (Graves') ophthalmopathy, and (v) parasellar region-associated adipose tissue in brain disorders. The therapy aspect of adipoparacrinology is also discussed.

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  • 1. Chaldakov GN, Fiore M, Ghenev PI, Stankulov IS, Aloe L. Atherosclerotic lesions: possible interactive involvement of intima, adventitia and associated adipose tissue. Int Med J 2000;7:43-9.
  • 2. Chaldakov GN, Stankulov IS, Hristova M, Ghenev PI. Adipobiology of disease: adipokines and adipokine-targeted pharmacology. Curr Pharm Des 2003;9:1023-31. [CrossRef]
  • 3. Töre F, Tonchev AB, Fiore M, Tuncel N, Atanassova P, Aloe L, et al. From adipose tissue protein secretion to adipopharmacology of disease. Immunol Endocr Metab Agents Med Chem 2007;7:149-55. [CrossRef]
  • 4. Chaldakov GN, Tonchev AB, Tuncel N, Atanassova P, Aloe L. Adipose tissue and mast cells: adipokines as Yin and Yang modulators of inflammation. In: G. Fantuzzi, T. Mazzone, editors. Nutrition and Health. Adipose Tissue and Adipokines in Health and Disease. Totowa, NJ, USA, Humana Press Inc 2006;12:147-54.
  • 5. Liu J, Divoux A, Sun J, Zhang J, Clément K, Glickman JN, et al. Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice. Nat Med 2009;15:940-5. [CrossRef]
  • 6. Ross R. Mechanisms of disease: Atherosclerosis - an inflammatory disease. N Engl J Med 1999;340:115-26. [CrossRef]
  • 7. Wilcox JN, Scott NA. Potential role of the adventitia in arteritis and atherosclerosis. Int J Cardiol 1996;54 (Suppl): S21-35. [CrossRef]
  • 8. Marchington JM, Mattacks CA, Pond CM. Adipose tissue in the mammalian heart and pericardium: structure, foetal development and biochemical properties. Comp Biochem Physiol (B) 1989;94:225-32. [CrossRef]
  • 9. Chaldakov GN, Stankulov IS, Aloe L. Subepicardial adipose tissue in human coronary atherosclerosis: another neglected phenomenon. Atherosclerosis 2001;154:237-8. [CrossRef]
  • 10. Chatterjee TK, Stoll LL, Denning GM, Harrelson A, Blomkalns AL, Idelman G, et al. Proinflammatory phenotype of perivascular adipocytes: influence of high-fat feeding. Circ Res 2009;104:541-9. [CrossRef]
  • 11. Vergahen SN, Visseren FLJ. Perivascular adipose tissue as a cause of atherosclerosis. Atherosclerosis 2011;214:3-10. [CrossRef]
  • 12. Chaldakov GN. Cardiovascular adipobiology: A novel. Heart-associated adipose tissue in cardiovascular disease. Ser J Exp Clin Res 2008;9:81-9.
  • 13. Chaldakov GN, Fiore M, Rancic G, Ghenev PI, Tuncel N, Beltowski J, et al. Rethinking vascular wall: periadventitial adipose tissue (tunica adiposa). Obes Metab 2010;6:46-9.
  • 14. Gao YJ. Dual modulation of vascular function by perivascular adipose tissue and its potential correlation with adiposity/ lipoatrophy-related vascular dysfunction. Curr Pharm Des 2007;13:2185-92. [CrossRef]
  • 15. Li FY, Cheng KK, Lam KS, Vanhoutte PM, Xu A. Cross-talk between adipose tissue and vasculature: role of adiponectin. Acta Phsysiol (Oxf) 2011;203:167-80. [CrossRef]
  • 16. Trayhurn P, de Heredia FP, Wang B, de Oliveira C, Gonzalez-Muniesa P, Wood IS. Cellular hypoxia: a key modulator of adipocyte function in obesity? Adipobiology 2009;1:19-26.
  • 17. Renes J, Rosenow A, Mariman E. Novel adipocyte features discovered by adipoproteomics. Adipobiology 2009;1:7-18.
  • 18. Fain JN, Sacks HS, Bahouth SW, Tichansky DS, Madan AK, Chemma PS. Human epicardial adipokine messenger RNAs: comparison of their expression in substernal, subcutaneous, and omental fat. Metabol Clin Exp 2010.
  • 19. Catalán V, Gómez-Ambrosi J, Rodríguez A, Ramírez B, Silva C, Rotellar F, et al. Increased adipose tissue expression of lipocalin-2 in obesity is related to inflammation and matrix metalloproteinase- 2 and metalloproteinase-9 activities in humans. J Mol Med (Berl) 2009;87:803-13. [CrossRef]
  • 20. Koenen TB, Stienstra R, van Tits LJ, Joosten LA, van Velzen JF, Hijmans A, et al. The inflammasome and caspase-1 activation: a new mechanism underlying increased inflammatory activity in human visceral adipose tissue. Endocrinology 2011;152:3769-78. [CrossRef]
  • 21. Frühbeck G. Vasoactive factors and inflammatory mediators produced in adipose tissue. In: Fantuzzi G, Mazzone T, editors. Health and Nutrition. Adipose Tissue and Adipokines in Health and Disease. Humana Press Inc, Totowa, NJ, USA, 2006; pp. 61-75.
  • 22. Yudkin JS, Eringa E, Stehouwer CD. “Vasocrine” signalling from perivascular fat: a mechanism linking insulin resistance to vascular disease. Lancet 2005;365:1817-20. [CrossRef]
  • 23. Fesüs G, Dubrovska G, Gorzelniak K, Kluge R, Huang Y, Luft FC, et al. Adiponectin is a novel humoral vasodilator. Cardiovasc Res 2007;75:719-27. [CrossRef]
  • 24. Wojcicka G, Jamroz-Wisniewska A, Attanasova P, Chaldakov GN, Chylinska-Kula B, Beltowski J. Differential effects of statins on endogenous H2S formation in perivascular adipose tissue. Pharmacol Res 2011;63:68-76. [CrossRef]
  • 25. Lu C, Su LY, Lee RM, Gao YJ. Mechanisms for perivascular adipose tissue-mediated potentiation of vascular contraction to perivascular neuronal stimulation: the role of adipocyte-derived angiotensin II. Eur J Pharmacol 2010;634:107-12. [CrossRef]
  • 26. Öhman MK, Luo W, Wang H, Guo C, Abdallah W, Russo HM, et al. Perivascular visceral adipose tissue induces atherosclerosis in apolipoprotein E deficient mice. Atherosclerosis 2011;219:33-9. [CrossRef]
  • 27. Tunçel N, Peker E, Şener E, Dal AG, Tunçel M, Chaldakov GN, et al. Cold exposure and adipose nitric oxide and mast cells: influence on aorta contractility. Adipobiology 2009;1:67-75.
  • 28. Rabkin SW. Epicardial fat: properties, function and relationship to obesity. Obesity 2007;8:253-61.
  • 29. Sacks HS, Fain JN. Human epicardial fat: what is new and what is missing? Clin Exp Pharmacol Physiol 2011;38:879-87. [CrossRef]
  • 30. Yorgun H, Canpolat U, Harzirolan T, Ateş AH, Sunman H, Dural M, et al. Increased epicardial fat tissue is a marker of metabolic syndrome in adult patients. Int J Cardiol 2011 Sep 16 (Epub ahead of print). [CrossRef] 31. Huang F, Lezama MA, Ontiveros JA, Bravo G, Villafafia S, del- Rio-Navarro BE, et al. Effect of losartan on vascular function in fructose-fed rats: the role of perivascular adipose tissue. Clin Exp Hypertens 2010;32:98-104. [CrossRef]
  • 32. Payne GA, Kohr MC, Tune JD. Epicardial perivascular adipose tissue as a therapeutic target in obesity-related coronary artery disease. Br J Pharmacol 2011;165:659-69. [CrossRef]
  • 33. Takaoka M, Nagata D, Kihara S, Shimomura I, Kimura Y, Tabata Y, et al. Periadventitial adipose tissue plays a critical role in vascular remodeling. Circ Res 2009;105:906-11. [CrossRef]
  • 34. Hausman GJ, Barb CR, Dean RG. Patterns of gene expression in pig adipose tissue: Insulin-like growth factor system proteins, neuropeptide Y (NPY), NPY receptors, neurotrophic factors and other secreted factors. Domest Anim Endocrinol 2008;35:24-34. [CrossRef]
  • 35. Sornelli F, Fiore M, Chaldakov GN, Aloe L. Brain-derived neurotrophic factor: a new adipokine. Biomed Rev 2007;18:65-8.
  • 36. Chaldakov GN, Fiore M, Stankulov IS, Manni L, Hristova MG, Antonelli A, et al. Neurotrophin presence in human coronary atherosclerosis and metabolic syndrome: a role for NGF and BDNF in cardiovascular disease? Prog Brain Res 2004;146:279-89. [CrossRef]
  • 37. Hiriart-Urdanivia M, Tableros VN, Velasco M, Larqué C, Cabrera- Vásquez S, Soto CS, et al. Insulin regulation in development and obesity. In: M Hiriart-Urdanivia and J Mas-Oliva, editors. Advances in obesity-diabetes research at UNAM. Manual Moderno, Mexico, D.F, 2010; pp 69-79.
  • 38. Manni L, Nikolova V, Vyagova D, Chaldakov GN, Aloe L. Reduced plasma levels of NGF and BDNF in patients with acute coronary syndromes. Int J Cardiol 2005;102:169-71. [CrossRef]
  • 39. Aloe L. Nerve growth factor, human skin ulcers and vascularization. Our experience. Prog Brain Res 2004;146:515-22. [CrossRef]
  • 40. Sacks HS. Weight loss in obesity reduces epicardial fat thickness; so what? J Appl Physiol 2009;106:1-2. [CrossRef]
  • 41. Schlett CL, Massaro JM, Lehman SJ, Bamberg F, O’Donnell CJ, Fox CS, et al. Novel measurements of periaortic adipose tissue in comparison to anthropometric measures of obesity, and abdominal adipose tissue. Int J Obes (Lond) 2009;33:226-32. [CrossRef]
  • 42. Skilton MR, Sérusclat A, Sethu AH, Brun S, Bernard S, Balkau B, et al. Noninvasive measurement of carotid extra-media thickness: associations with cardiovascular risk factors and intima-media thickness. JACC Cardiovasc Imaging 2009;2:176-82. [CrossRef]
  • 43. Dashwood MR, Dooley A, Shi-Wen X, Abraham DJ, Souza DS. Does periadventitial fat-derived nitric oxide play a role in improved saphenous vein graft patency in patients undergoing coronary artery bypass surgery? J Vasc Res 2007;44:175-81. [CrossRef]
  • 44. Malinowski M, Deja MA, Golba KS, Roleder T, Biernat J, Woś S. Perivascular tissue of internal thoracic artery releases potent nitric oxide and prostacyclin-independent anticontractile factor. Eur J Cardiothorac Surg 2008;33:225-31. [CrossRef]
  • 45. Feng Y, Gordts SC, Chen F, Hu Y, Van Craeyveld E, Jacobs F, et al. Topical HDL administration reduces vein graft atherosclerosis in apo E deficient mice. Atherosclerosis 2011;214:271-8. [CrossRef]
  • 46. Shimomura I, Hammer RE, Richardson JA, Ikemo S, Bashmakov Y, Goldstein JL, et al. Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy. Genes Dev 1998;12:3162-94. [CrossRef]
  • 47. McDaniel SM, Rumer KK, Biroc SL, Metz RP, Singh M, Porter W, et al. Remodeling of the mammary microenvironment after lactation promotes breast tumor cell metastasis. Am J Pathol 2006;168:608-20. [CrossRef]
  • 48. Celis JE, Moreira JM, Cabezon T, Gromov P, Friis E, Rank F, Gromova I. Identification of extracellular and intracellular signaling components of the mammary adipose tissue and its interstitial fluid in high risk breast cancer patients: toward dissecting the molecular circuitry of epithelial-adipocyte stromal cell interactions. Mol Cell Proteomics 2005;4:492-522. [CrossRef]
  • 49. Subbaramaiah K, Howe LR, Bhardwaj P, Du B, Zhou XK, Blaho VA, et al. Obesity is associated with inflammation and elevated aromatase expression in the mouse mammary gland. Cancer Prev Res (Phila) 2011;4:329-46. [CrossRef]
  • 50. Kashiwase Y, Morioka J, Inamura H, Yoshizawa Y, Usui R, Kurosawa M. Quantitative analysis of mast cells in benign and malignant breast lesions. Immunohistochemical study on formalinfixed, paraffin-embedded tissues. Int Arch Allergy Immunol 2004;134:199-205. [CrossRef]
  • 51. Dollé L, Adriaenssens E, El Yazidi-Belkoura I, Le Bourhis X, Nurcombe V, Hondermarck H. Nerve growth factor receptors and signaling in breast cancer. Curr Cancer Drug Targets 2004;4:463- 740. [CrossRef]
  • 52. Vanhecke E, Adriaenssens E, Verbeke S, Meignan S, Germain E, Berteaux N, et al. Brain-derived neurotrophic factor and neurotrophin- 4/5 are expressed in breast cancer and can be targeted to inhibit tumor cell survival. Clin Cancer Res 2011;17:1741-52. [CrossRef]
  • 53. Romon R, Adriaenssens E, Lagadec C, Germain E, Hondermarck H, Le Bourhis X. Nerve growth factor promotes breast cancer angiogenesis by activating multiple pathways. Mol Cancer 2010;9:157. [CrossRef]
  • 54. Chiarenza A, Lazarovici P, Lempereur L, Cantarella G, Bianchi A, Bernardini R. Tamoxifen inhibits nerve growth factor-induced proliferation of the human breast cancerous cell line MCF-7. Cancer Res 2001;61:3002-8.
  • 55. Finley DS, Calvert VS, Inokuchi J, Lau A, Narula N, Petricoin EF, et al. Periprostatic adipose tissue as a modulator of prostate cancer aggressiveness. J Urol 2009;182:1621-7. [CrossRef]
  • 56. van Roermund JG, Hinnen KA, Tolman CJ, Bol GH, Witjes JA, Bosch JL, et al. Periprostatic fat correlates with tumour aggressiveness in prostate cancer patients. BJU Int 2011;107:1775-9. [CrossRef]
  • 57. van Roermund JG, Bol GH, Witjes JA, Ruud Bosch JL, Kiemeney LA, van Vulpen M. Periprostatic fat measured on computed tomography as a marker for prostate cancer aggressiveness. World J Urol 2010;28:699-704. [CrossRef]
  • 58. Warrington RJ, Lewis KE. Natural antibodies against nerve growth factor inhibit in vitro prostate cancer cell metastasis. Cancer Immunol Immunother 2011;60:187-95. [CrossRef]
  • 59. Jimenez-Andrade JM, Ghilardi JR, Castañeda-Corral G, Kuskowski MA, Mantyh PW. Preventive or late administration of anti-NGF therapy attenuates tumor-induced nerve sprouting, neuroma formation, and cancer pain. Pain 2011;152:2564-74. [CrossRef]
  • 60. Watanabe T, Inoue M, Sasaki K, Araki M, Uehara S, Monden K, et al. Nerve growth factor level in the prostatic fluid of patients with chronic prostatitis/chronic pelvic pain syndrome is correlated with symptom severity and response to treatment. BJU Int 2011;108:248-51. [CrossRef]
  • 61. Rende M, Rambotti MG, Stabile AM, Pistilli A, Montagnoli C, Chiarelli MT, et al. Novel localization of low affinity NGF receptor (p75) in the stroma of prostate cancer and possible implication in neoplastic invasion: an immunohistochemical and ultracytochemical study. Prostate 2010;70:555-61.
  • 62. Festuccia C, Muzi P, Gravina GL, Millimaggi D, Speca S, Dolo V, et al. Tyrosine kinase inhibitor CEP-701 blocks the NTRK1/NGF receptor and limits the invasive capability of prostate cancer cells in vitro. Int J Oncol 2007;30:193-200.
  • 63. Goda M, Atagi S, Amitani K, Hobara N, Kitamura Y, Kawasaki H. Nerve growth factor suppresses prostate tumor growth. J Pharmacol Sci 2010;112:463-6. [CrossRef]
  • 64. Thomas EL, Parkinson JR, Frost GS, Goldstone AP, Doré CJ, Mc- Carthy JP, et al. The missing risk: MRI and MRS phenotyping of abdominal adiposity and ectopic fat. Obesity (Silver Spring) 2012;20:76-87. [CrossRef]
  • 65. Sacks HS, Fain JN, Holman B, Cheema P, Chary A, Parks F, et al. Uncoupling protein-1 and related messenger ribonucleic acids in human epicardial and other adipose tissues: epicardial fat functioning as brown fat. J Clin Endocrinol Metab 2009;94:3611-5. [CrossRef]
  • 66. Pond CM. HIV-associated adipose redistribution syndrome. Trends Immunol 2003;1:13-8. [CrossRef]
  • 67. Pond CM. Paracrine provision of lipids in the immune system. Cur Immunol Rev 2009;5:150-60. [CrossRef]
  • 68. Cannady WE, Brann DW, Mahesh VB. The potential role of periovarian fat and leptin in initiation of puberty in the immature rat. Int J Obes Relat Metab Disord 2000;24:S146-7. [CrossRef]
  • 69. Weninger WJ, Prokop M. In vivo 3D analysis of the adipose tissue in the orbital apex and the compartments of the parasellar region. Clin Anat 2004;17:112-7. [CrossRef]
  • 70. Atanassova P, Tonchev AB, Peneva VN, Chaldakov GN, Fiore M, Aloe L. What are subcutaneous adipocytes really good fo? Exp Dermatol 2007;16:55-8.
  • 71. Distel E, Cadoudal T, Durant S, Poignard A, Chevalier X, Benelli C. The infrapatellar fat pad in knee osteoarthritis: an important source of interleukin-6 and its soluble receptor. Arthritis Rheum 2009;60:3374-7. [CrossRef]
  • 72. Chen MH, Chen MH, Liao SL, Chang TC, Chuang LM. Role of macrophage infiltration in the orbital fat of patients with Graves’ ophthalmopathy. Clin Endocrionol (Oxf) 2008;69:332-7. [CrossRef]
  • 73. Reina MA, Franco CD, López A, Dé Andrés JA, van Zundert A. Clinical implications of epidural fat in the spinal canal. A scanning electron microscopic study. Acta Anaesthesiol Belg 2009;60:7-17.
  • 74. Gómez R, Conde J, Scotece M, Gómez-Reino JJ, Lago F, Gualillo O. What’s new in our understanding of the role of adipokines in rheumatic diseases? Nat Rev Rheumatol 2011;7:528-36. [CrossRef]
  • 75. Duhne M, Velasco M, Larque, Gutiérrez G, Robles G, Hiriart M. Nerve growth factor, pancreatic beta cells, adipose tissue and diabetes mellitus. [Abstract]. Adipobiology 2009;1:117.
  • 76. Fox CS, Massaro JM, Schlett CL, Lehman SJ, Meigs JB, O’Donnell CJ, et al. Periaortic fat deposition is associated with peripheral arterial disease: the Framingham heart study. Circ Cardiovasc Imaging 2010;3:515-9. [CrossRef]
  • 77. Sumitomo M, Asakuma J, Yoshii H, Sato A, Horiguchi A, Ito K, et al. Anterior perirectal fat tissue thickness is a strong predictor of recurrence after high-intensity focused ultrasound for prostate cancer. Int J Urol 2010;17:776-82. [CrossRef]
  • 78. Liu YP, Li SZ, Yuan F, Xia J, Yu X, Liu X, et al. Infrapatellar fat pad may be with tendon repairing ability and closely related with the developing process of patella Baja. Med Hypotheses 2011;77:620-3. [CrossRef]
  • 79. Klein-Wieringa IR, Kloppenburg M, Bastiaansen-Jenniskens YM, Yusuf E, Kwekkeboom JC, El-Bannoudi H, et al. The infrapatellar fat pad of patients with osteoarthritis has an inflammatory phenotype. Ann Rheum Dis 2011;70:851-7. [CrossRef]
  • 80. Wilcox JN, Okamoto EI, Nakahara KI, Vinten-Johansen J. Perivascular responses after angioplasty which may contribute to postangioplasty restenosis: a role for circulating myofibroblast precursors? Ann NY Acad Sci 2001;947:68-90. [CrossRef]
  • 81. Rancic G, Petrovic A, Sekulovic-Stefanovic L, Bojanic V, Ghenev PI. Adipotopography: TOFI versus TOTI, or a hidden Homo obesus. The First International Symposim on Adipobiology and Adipopharmacology, 20 October 2007, Varna, Bulgaria. pp 13-14A.
Balkan Medical Journal-Cover
  • ISSN: 2146-3123
  • Başlangıç: 2015
  • Yayıncı: Erkan Mor
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