Skip to main content

Advertisement

Log in

Epicardial Fat from Guinea Pig: A Model to Study the Paracrine Network of Interactions between Epicardial Fat and Myocardium?

  • Published:
Cardiovascular Drugs and Therapy Aims and scope Submit manuscript

Abstract

Background

Epicardial adipose tissue (Epi) is a fat depot which is closely apposed on the myocardium. Several lines of evidence suggest that it is not only a lipid-storing depot, but also an active endocrine organ which secrets inflammatory cytokines and chemolines as suggested for other types of visceral fat.

Objectives and methods

We selected guinea pigs which have been shown to expand Epi with age, to investigate the expansion and properties of Epi and its impact on cardiac structure and function in detail.

Results

The amount of epicardial fat increases rapidly with age and accumulates at the aortic arch. It extends over the anterior surface of both ventricles and along the anterior and posterior branches of the coronary arteries. It also expands within the epicardium. The pattern of cytokines released by Epi is altered with age showing an up- and down-regulation of a variety of the 120 cytokines analyzed. Most prominently changed are IGFBP-4 and TIMP-2, whereas the release of adiponectin is not modified by age.

Conclusions

The amount of Epi is closely correlated to the amount of other types of visceral fat, to insulin resistance and other features of the metabolic syndrome, but also to cardiac hypertrophy and cardiac dysfunction. The data provide evidence that the guinea pig heart is a suitable model to analyze the interactions between Epi, heart vessels and muscle tissue. It allows identifying the influence of nutritional and metabolic alterations on the complexity of the network of locally released mediators for heart structure and function. A deeper understanding of this animal model may be helpful to analyze the interactions between Epi and the myocardium in humans—where the availability of tissue and the possibilities to modify nutritional and metabolic influences on heart are restricted—and the impact of Epi on cardiovascular risk.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Rabkin SW. Epicardial fat: properties, function and relationship to obesity. Obes Rev. 2007;8:253–61.

    Article  PubMed  CAS  Google Scholar 

  2. Sacks HS, Fain JN. Human epicardial adipose tissue: a review. Am Heart J. 2007;153:907–17.

    Article  PubMed  CAS  Google Scholar 

  3. Wellen KE, Hotamisligil GS. Obesity-induced inflammatory changes in adipose tissue. J Clin Invest. 2003;112:1785–8.

    PubMed  CAS  Google Scholar 

  4. Xu H, Barnes GT, Yang Q, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003;112:1821–30.

    PubMed  CAS  Google Scholar 

  5. Willis RA. The anatomic examination of the body of Thomas Par. The works of William Harvey. London: Sydenham Society; 1847. p. 587–92.

    Google Scholar 

  6. Bedford E. The story of fatty heart. A disease of Victorian times. Brit Heart J. 1972;34:23–8.

    Article  PubMed  CAS  Google Scholar 

  7. Iacobellis G, Corradi D, Sharma AM. Epicardial adipose tissue: anatomic, biomolecular and clinical relationships with the heart. Nat Clin Pract Cardiovasc Med. 2005;2:536–43.

    Article  PubMed  Google Scholar 

  8. Iacobellis G, Ribaudo MC, Assael F, et al. 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;88:5163–8.

    Article  PubMed  CAS  Google Scholar 

  9. Iacobellis G, Assael F, Ribaudo MC, et al. Epicardial fat from echocardiography: a new method for visceral adipose tissue prediction. Obes Res. 2003;11:304–10.

    PubMed  Google Scholar 

  10. Iacobellis G. Imaging of visceral adipose tissue: an emerging diagnostic tool and therapeutic target. Curr Drug Targets Cardiovasc Haematol Disord. 2005;5:345–53.

    Article  PubMed  CAS  Google Scholar 

  11. Iacobellis G, Leonetti F. Epicardial adipose tissue and insulin resistance in obese subjects. J Clin Endocrinol Metab. 2005;90:6300–2.

    Article  PubMed  CAS  Google Scholar 

  12. Iacobellis G, Ribaudo MC, Zappaterreno A, et al. Relation between epicardial adipose tissue and left ventricular mass. Am J Cardiol. 2004;94:1084–7.

    Article  PubMed  Google Scholar 

  13. Iacobellis G, Ribaudo MC, Zappaterreno A, et al. Relationship of insulin sensitivity and left ventricular mass in uncomplicated obesity. Obes Res. 2003;11:518–24.

    Article  PubMed  Google Scholar 

  14. Iacobellis G, Leonetti F, Singh N, et al. Relationship of epicardial adipose tissue with atrial dimensions and diastolic function in morbidly obese subjects. Int J Cardiol. 2007;115:272–3.

    Article  PubMed  Google Scholar 

  15. 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.

    Article  PubMed  CAS  Google Scholar 

  16. Fernandez ML, Volek JS. Guinea pigs: A suitable animal model to study lipoprotein metabolism, atherosclerosis and inflammation. Nutr Metab (Lond). 2006;3:17.

    Article  CAS  Google Scholar 

  17. Fernandez ML. Guinea pigs as models for cholesterol and lipoprotein metabolism. J Nutr. 2001;131:10–20.

    PubMed  CAS  Google Scholar 

  18. Tomanek RJ, Searls JC, Lachenbruch PA. Quantitative changes in the capillary bed during developing, peak, and stabilized cardiac hypertrophy in the spontaneously hypertensive rat. Circ Res. 1982;51:295–304.

    PubMed  CAS  Google Scholar 

  19. Loud AV, Beghi C, Olivetti G, et al. Morphometry of right and left ventricular myocardium after strenuous exercise in preconditioned rats. Lab Invest. 1984;51:104–11.

    PubMed  CAS  Google Scholar 

  20. Rösen P, Kiesel U, Reinauer H, et al. Cardiopathy in the spontaneously diabetic (BB) rat. evidence for microangiopathy and autonomic neuropathy in the diabetic heart. In: Nagano M, Dhalla N, editors. The diabetic heart. New York: Raven; 1991. p. 145–57.

    Google Scholar 

  21. Sasson S, Eckel J. Disparate effects of 12-lipoxygenase and 12-hydroxyeicosatetraenoic acid in vascular endothelial and smooth muscle cells and in cardiomyocytes. Arch Physiol Biochem. 2006;112:119–29.

    Article  PubMed  CAS  Google Scholar 

  22. Vahsen S, Rakowski K, Ledwig D, et al. Altered GLUT4 translocation in skeletal muscle of 12/15-lipoxygenase knockout mice. Horm Metab Res. 2006;38:391–6.

    Article  PubMed  CAS  Google Scholar 

  23. Despres JP. Is visceral obesity the cause of the metabolic syndrome? Ann Med. 2006;38:52–63.

    Article  PubMed  CAS  Google Scholar 

  24. Sharma AM, Chetty VT. Obesity, hypertension and insulin resistance. Acta Diabetol. 2005;42:S3–S8.

    Article  PubMed  CAS  Google Scholar 

  25. Kankaanpaa M, Lehto HR, Parkka JP, et al. Myocardial triglyceride content and epicardial fat mass in human obesity: relationship to left ventricular function and serum free fatty acid levels. J Clin Endocrinol Metab. 2006;91:4689–95.

    Article  PubMed  CAS  Google Scholar 

  26. Zhou YT, Grayburn P, Karim A, et al. Lipotoxic heart disease in obese rats: implications for human obesity. Proc Natl Acad Sci U S A. 2000;97:1784–89.

    Article  PubMed  CAS  Google Scholar 

  27. Taegtmeyer H, McNulty P, Young ME. Adaptation and maladaptation of the heart in diabetes: Part I: general concepts. Circulation. 2002;105:1727–33.

    Article  PubMed  CAS  Google Scholar 

  28. Young ME, McNulty P, Taegtmeyer H. Adaptation and maladaptation of the heart in diabetes: Part II: potential mechanisms. Circulation. 2002;105:1861–70.

    Article  PubMed  CAS  Google Scholar 

  29. Iacobellis G, Leonetti F, Singh N, et al. Relationship of epicardial adipose tissue with atrial dimensions and diastolic function in morbidly obese subjects. Int J Cardiol. 2006;15:272–3.

    Google Scholar 

  30. Basso C, Thiene G. Adipositas cordis, fatty infiltration of the right ventricle, and arrhythmogenic right ventricular cardiomyopathy. Just a matter of fat? Cardiovasc Pathol. 2005;14:37–41.

    Article  PubMed  Google Scholar 

  31. Iacobellis G, Pistilli D, Gucciardo M, et al. Adiponectin expression in human epicardial adipose tissue in vivo is lower in patients with coronary artery disease. Cytokine. 2005;29:251–5.

    PubMed  CAS  Google Scholar 

  32. Iacobellis G, Pellicelli AM, Sharma AM, et al. Relation of subepicardial adipose tissue to carotid intima-media thickness in patients with human immunodeficiency virus. Am J Cardiol. 2007;99:1470–2.

    Article  PubMed  Google Scholar 

  33. Iacobellis G, Sharma AM, Pellicelli AM, et al. Epicardial adipose tissue is related to carotid intima-media thickness and visceral adiposity in HIV-infected patients with highly active antiretroviral therapy-associated metabolic syndrome. Curr HIV Res. 2007;5:275–9.

    Article  PubMed  CAS  Google Scholar 

  34. Baker AR, Silva NF, Quinn DW, et al. Human epicardial adipose tissue expresses a pathogenic profile of adipocytokines in patients with cardiovascular disease. Cardiovasc Diabetol. 2006;5:1.

    Article  PubMed  CAS  Google Scholar 

  35. Mazurek T, Zhang L, Zalewski A, et al. Human epicardial adipose tissue is a source of inflammatory mediators. Circulation. 2003;108:2460–6.

    Article  PubMed  Google Scholar 

  36. Dietze D, Koenen M, Rohrig K, et al. Impairment of insulin signaling in human skeletal muscle cells by co-culture with human adipocytes. Diabetes. 2002;51:2369–76.

    Article  PubMed  CAS  Google Scholar 

  37. Gabella G. Cardiovascular system. In: Williams P, editor. Gray’s anatomy 38th edn. Edingburgh: Churchill Livingstone; 1995. p. 1445.

    Google Scholar 

  38. Tansey DK, Aly Z, Sheppard MN. Fat in the right ventricle of the normal heart. Histopathology. 2005;46:98–104.

    Article  PubMed  CAS  Google Scholar 

  39. Hotamisligil GS, Spiegelman BM. Tumor necrosis factor alpha: a key component of the obesity-diabetes link. Diabetes. 1994;43:1271–8.

    Article  PubMed  CAS  Google Scholar 

  40. Scherer PE. Adipose tissue: from lipid storage compartment to endocrine organ. Diabetes. 2006;55:1537–45.

    Article  PubMed  CAS  Google Scholar 

  41. Nguyen-Duy TB, Nichaman MZ, Church TS, et al. Visceral fat and liver fat are independent predictors of metabolic risk factors in men. Am J Physiol Endocrinol Metab. 2003;284:E1065–E1071.

    PubMed  CAS  Google Scholar 

  42. Grimble RF. Genotypic influences on metabolic alterations during inflammation and the nutritional outcome. Nestle Nutr Workshop Ser Clin Perform Programme. 2002;7:1–13.

    PubMed  CAS  Google Scholar 

  43. Grimble RF. Inflammatory status and insulin resistance. Curr Opin Clin Nutr Metab Care. 2002;5:551–9.

    Article  PubMed  CAS  Google Scholar 

  44. Yudkin JS, Eringa E, Stehouwer CD. “Vasocrine” signalling from perivascular fat: a mechanism linking insulin resistance to vascular disease. Lancet. 2005;365:1817–20.

    Article  PubMed  Google Scholar 

  45. Galili O, Versari D, Sattler KJ, et al. Early experimental obesity is associated with coronary endothelial dysfunction and oxidative stress. Am J Physiol Heart Circ Physiol. 2007;292:H904–H911.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

We thank D.Herzfeld and H.Müller for their skillful technical assistance.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Peter Rösen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Swifka, J., Weiß, J., Addicks, K. et al. Epicardial Fat from Guinea Pig: A Model to Study the Paracrine Network of Interactions between Epicardial Fat and Myocardium?. Cardiovasc Drugs Ther 22, 107–114 (2008). https://doi.org/10.1007/s10557-008-6085-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10557-008-6085-z

Key words

Navigation