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Horm Metab Res 2008; 40(7): 442-445
DOI: 10.1055/s-2008-1062724
Hypothesis

© Georg Thieme Verlag KG Stuttgart · New York

The Double Role of Epicardial Adipose Tissue as Pro- and Anti-inflammatory Organ

G. Iacobellis 1 , G. Barbaro 2
  • 1Endocrinology, Department of Medicine, McMaster University, Hamilton, ON, Canada
  • 2Cardiology Unit, Department of Medical Pathophysiology, University “La Sapienza”, Rome, Italy
Further Information

Publication History

received 25.10.2007

accepted 29.11.2007

Publication Date:
13 March 2008 (online)

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Abstract

Obesity is associated with low grade inflammation. Whether this is just an adaptive response to excess adiposity to maintain a normal oxygen supply or a chronic activation of the innate immune system is still unknown. Recent research has focused on the origin of the inflammatory markers in obesity and the extent to which adipose tissue has a direct effect. The production of adipokines by visceral adipose tissue is of particular interest since their local secretion by visceral fat depots may provide a novel mechanistic link between obesity and the associated vascular complications. Growing evidences suggest that the epicardial adipose tissue, the visceral fat depot located around the heart, may locally interact with myocardium and coronary arteries. Epicardial fat is a source of adiponectin and adrenomedullin, adipokines with anti-inflammatory properties, and several proinflammatory cytokines as well as Tumor Necrosis Factor-alpha (TNF-α), Interleukin 1 (IL1), IL-1 h, Interleukin (IL6), Monocyte Chemoattractive Protein-1 (MCP-1), Nerve Growth Factor (NGF), resistin, Plasminogen Activator Inhibitor-1 (PAI-1), and free fatty acids. Epicardial adipose tissue could locally modulate the heart and vasculature, through paracrine secretion of pro- and anti-inflammatory cytokines, thereby playing a possible role in the adiposity-related inflammation and atherosclerosis. On the other hand, epicardial fat could exert a protective effect through adiponectin and adrenomedullin secretion as response to local or systemic metabolic or mechanical insults. Future studies will continue to provide new and fascinating insights into the double role of epicardial adipose tissue in the development of cardiovascular pathology and/or in protecting the heart and arteries.

Key words

epicardial fat - epicardial adipose tissue - obesity - visceral adiposity - inflammation

References

  • 1 Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events.  N Engl J Med. 2002;  347 1557-1565
    CrossrefPubMedSearch in Google Scholar
  • 2 Bastard JP, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H, Capeau J, Feve B. Recent advances in the relationship between obesity, inflammation, and insulin resistance.  Eur Cytokine Netw. 2006;  17 4-12
    PubMedSearch in Google Scholar
  • 3 Karelis AD, Faraj M, Bastard JP, St-PierreH DH, Brochu M, Prud’homme D, Rabasa-Lhoret R. The metabolically healthy, but obese individual presents a favorable inflammation profile.  J Clin Endocrinol Metab. 2005;  90 4145-4150
    CrossrefPubMedSearch in Google Scholar
  • 4 Tilg H, Moschen AR. Adipocytokines: mediators linking adipose tissue, inflammation and immunity.  Nat Rev Immunol. 2006;  6 772-783
    CrossrefPubMedSearch in Google Scholar
  • 5 Trayhurn P, Wood IS. Adipokines: inflammation and the pleiotropic role of white adipose tissue.  Br J Nutr. 2004;  92 347-355
    CrossrefPubMedSearch in Google Scholar
  • 6 Kyrou I, Tsigos C. Stress mechanisms and metabolic complications.  Horm Metab Res. 2007;  39 430-438
    Thieme ConnectPubMedSearch in Google Scholar
  • 7 Fischer-Posovszky P, Wabitsch M, Hochberg Z. Endocrinology of Adipose Tissue – An Update.  Horm Metab Res. 2007;  39 314-321
    Thieme ConnectPubMedSearch in Google Scholar
  • 8 Juge-Aubry CE, Henrichot E, Meier CA. Adipose tissue: a regulator of inflammation.  Best Pract Res Clin Endocrinol Metab. 2005;  19 547-566
    CrossrefPubMedSearch in Google Scholar
  • 9 Rodriguez A, Catalan V, Gomez-Ambrosi J, Fruhbeck G. Visceral and subcutaneous adiposity: are both potential therapeutic targets for tackling the metabolic syndrome?.  Curr Pharm Des. 2007;  13 2169-2175
    CrossrefPubMedSearch in Google Scholar
  • 10 Pou KM, Massaro JM, Hoffmann U, Vasan RS, Maurovich-Horvat P, Larson MG, Keaneyr  Jr  JF, Meigs JB, Lipinska I, Kathiresan S, Murabito JM, O’donnell CJ, Benjamin EJ, Fox CS. Visceral and subcutaneous adipose tissue volumes are cross-sectionally related to markers of inflammation and oxidative stress: the framingham heart study.  Circulation. 2007;  116 1234-1241
    CrossrefPubMedSearch in Google Scholar
  • 11 Yudkin JS. Inflammation, obesity, and the metabolic syndrome.  Horm Metab Res. 2007;  39 707-709
    Thieme ConnectPubMedSearch in Google Scholar
  • 12 Fruhbeck G. The adipose tissue as a source of vasoactive factors.  Curr Med Chem Cardiovasc Hematol Agents. 2004;  2 197-208
    CrossrefPubMedSearch in Google Scholar
  • 13 Guzik TJ, Mangalat D, Korbut R. Adipocytokines – novel link between inflammation and vascular function?.  J Physiol Pharmacol. 2006;  57 505-528
    PubMedSearch in Google Scholar
  • 14 Berg AH, Scherer PE. Adipose tissue, inflammation, and cardiovascular disease.  Circ Res. 2005;  96 939-949
    CrossrefPubMedSearch in Google Scholar
  • 15 Iacobellis G, Corradi D, Sharma AM. Epicardial adipose tissue: anatomic, biomolecular and clinical relationships with the heart.  Nat Clin Pract Cardiovasc Med. 2005;  2 536-543
    CrossrefPubMedSearch in Google Scholar
  • 16 Iacobellis G, Pond CM, Sharma AM. Different “weight” of cardiac and general adiposity in predicting left ventricle morphology.  Obesity. 2006;  14 1679-1684
    CrossrefPubMedSearch in Google Scholar
  • 17 Sacks HS, Fain JN. Human epicardial adipose tissue: a review.  Am Heart J. 2007;  153 907-917
    CrossrefPubMedSearch in Google Scholar
  • 18 Schejbal V. Epicardial fatty tissue of the right ventricle: morphology, morphometry and functional significance.  Pneumologie. 1989;  43 490-499
    PubMedSearch in Google Scholar
  • 19 Corradi D, Maestri R, Callegari S. The ventricular epicardial fat is related to the myocardial mass in normal, ischemic and hypertrophic hearts.  Cardiovasc Pathol. 2004;  13 313-316
    CrossrefPubMedSearch in Google Scholar
  • 20 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;  94 225-232
    CrossrefPubMedSearch in Google Scholar
  • 21 Marchington JM, Pond CM. Site specific properties of pericardial and epicardial adipose tissue: the effects of insulin and high-fat feeding on lipogenesis and the incorporation of fatty acids in vivo.  Int J Obesity. 1990;  14 1013-1022
    PubMedSearch in Google Scholar
  • 22 Kankaanpaa M, Lehto HR, Parkka J, Komu P, Viljanen A, Ferrannini E, Knuuti J, Nuutila P, Parkkola R, Iozzo P. Myocardial triglyceride content and epicardial adipose mass in human obesity: relationship to left ventricular function and serum free fatty acid levels.  J Clin Endocrinol Metab. 2006;  91 4689-4695
    CrossrefPubMedSearch in Google Scholar
  • 23 Iacobellis G, Pistilli D, Gucciardo M. Adiponectin expression in human epicardial adipose tissue in vivo is lower in patients with coronary artery disease.  Cytokine. 2005;  29 251-255
    PubMedSearch in Google Scholar
  • 24 Mazurek T, Zhang L, Zalewski A. Human epicardial adipose tissue is a source of inflammatory mediators.  Circulation. 2003;  108 2460-2466
    CrossrefPubMedSearch in Google Scholar
  • 25 Kremen J, Dolinkova M, Krajickova J. et al . Increased subcutaneous and epicardial adipose tissue production of proinflammatory cytokines in cardiac surgery patients: possible role in postoperative insulin resistance.  J Clin Endocrinol Metab. 2006;  91 4620-4627
    CrossrefPubMedSearch in Google Scholar
  • 26 Chaldakov GN, Fiore M, Stankulov IS, Manni L, Hristova MG, Antonelli A, Ghenev PI, Aloe L. Neurotrophin presence in human coronary atherosclerosis and metabolic syndrome: a role for NGF and BDNF in cardiovascular disease?.  Prog Brain Res. 2004;  146 279-289
    PubMedSearch in Google Scholar
  • 27 Baker AR, Silva NF, Quinn DW, Harte AL, Pagano D, Bonser RS, Kumar S, MacTernan PG. Human epicardial adipose tissue expresses a pathogenic profile of adipocytokines in patients with cardiovascular disease.  Cardiovasc Diabetol. 2006;  5 1-7
    CrossrefPubMedSearch in Google Scholar
  • 28 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 43-49
    PubMedSearch in Google Scholar
  • 29 Silaghi A, Achard V, Paulmyer-Lacroix O, Scridon T, Tassistro V, Duncea I, Clément K, Dutour A, Grino M. Expression of adrenomedullin in human epicardial adipose tissue: role of coronary status.  Am J Physiol Endocrinol Metab. 2007;  293 E1443-E1450
    CrossrefPubMedSearch in Google Scholar
  • 30 Iacobellis G, Assael F, Ribaudo MC, Zappaterreno A, Alessi G, Mario U Di, Leonetti F. Epicardial fat from echocardiography: a new method for visceral adipose tissue prediction.  Obes Res. 2003;  11 304-310
    CrossrefPubMedSearch in Google Scholar
  • 31 Iacobellis G, Ribaudo MC, Assael F, Vecci E, Tiberti C, Zappaterreno A, Mario U Di, Leonetti F. Echocardiographic epicardial adipose tissue is related to anthropometric and clinical parameters of metabolic syndrome: a new indicator of cardiovascular risk.  J Clin Endocrinol Metab. 2003;  88 5163-5168
    CrossrefPubMedSearch in Google Scholar
  • 32 Iacobellis G, Ribaudo MC, Zappaterreno A, Iannucci CV, Leonetti F. Relation between epicardial adipose tissue and left ventricular mass.  Am J Cardiol. 2004;  94 1084-1087
    CrossrefPubMedSearch in Google Scholar
  • 33 Iacobellis G, Leonetti F. Epicardial adipose tissue and insulin resistance in obese subjects.  J Clin Endocrinol Metab. 2005;  90 6300-6302
    CrossrefPubMedSearch in Google Scholar
  • 34 Iacobellis G, Pellicelli AM, Sharma AM, Grisorio B, Barbarini G, Barbaro G. Relation of subepicardial adipose tissue to carotid intima-media thickness in patients with human immunodeficiency virus.  Am J Cardiol. 2007;  99 1470-1472
    CrossrefPubMedSearch in Google Scholar
  • 35 Jeong JW, Jeong MH, Yun KH, Oh SK, Park EM, Kim YK, Rhee SJ, Lee EM, Lee J, Yoo NJ, Kim NH, Park JC. Echocardiographic epicardial fat thickness and coronary artery disease.  Circ J. 2007;  71 536-539
    CrossrefPubMedSearch in Google Scholar
  • 36 Ahn SG, Lim HS, Joe DY, Kang SJ, Choi BJ, Choi SY, Yoon MH, Hwang GS, Tahk SJ, Shin JH. Relationship of epicardial adipose tissue by echocardiography to coronary artery disease.  Heart. 2008;  94 e7
    CrossrefPubMedSearch in Google Scholar
  • 37 Frayn KN, Tan GD, Karpe F. Adipose tissue: a key target for diabetes pathophysiology and treatment?.  Horm Metab Res. 2007;  39 739-742
    Thieme ConnectPubMedSearch in Google Scholar
  • 38 Iacobellis G, Sharma AM. Epicardial adipose tissue as new cardio-metabolic risk marker and potential therapeutic target in the metabolic syndrome.  Curr Pharm Des. 2007;  13 2180-2184
    CrossrefPubMedSearch in Google Scholar

Correspondence

G. IacobellisMD, PhD 

Department of Medicine

St. Joseph's Hospital

50 Charlton Avenue East

5th Fontbonne Bldg

Hamilton

Ontario

Canada L8N 4A6

Phone: +1/905/521 60 53

Fax: +1/905/540 65 96

Email: gianluca@ccc.mcmaster.ca

Email: gianluca.iaco@tin.it