Effects of Obesity and Adiposity on Cardiac Mechanical Properties

Yau-Huei Lai, Kuo-Tzu Sung, Chung-Lieh Hung, Jen-Yuan Kuo

Yau-Huei Lai, Kuo-Tzu Sung, Chung-Lieh Hung, Jen-Yuan Kuo, Division of Cardiology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
Yau-Huei Lai, Kuo-Tzu Sung, Chung-Lieh Hung, Jen-Yuan Kuo, Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan
Yau-Huei Lai, Kuo-Tzu Sung, Chung-Lieh Hung, Jen-Yuan Kuo, Mackay Medical College, Taipei, Taiwan

Correspondence to: Jen-Yuan Kuo, Division of Cardiology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
Email: jykuo5813@gmail.com
Telephone: +886-2-2543-3535
Fax: +886-2-2543-3642
Received: April 29, 2014
Revised: July 31, 2014
Accepted: August 5, 2014
Published online: September 19, 2014


Metabolic abnormalities accompanied by excessive body fat and systemic inflammation can lead to higher incidence of heart failure. Obesity is associated with altered cardiac remodeling, possibly due to increased hemodynamic load, neurohormonal activation, and increased cytokine production. Through direct quantification of visceral adipose tissues surrounding vital organs, especially the epicardial adipose tissue, investigators have demonstrated the link between its activity and adverse cardiovascular events.

Key words: Obesity, Epicardial fat, Cardiac Dysfunction, Inflammation

© 2014 The Authors. Published by ACT Group Ltd.

Laia YH, Sunga KT, Kuoa JY, Hung CL. Effects of Obesity and Adiposity on Cardiac Mechanical Properties. Journal of Cardiology and Therapy 2014; 1(8): 176-180 Available from: URL: http://www.ghrnet.org/index.php/jct/article/view/863


The long-term deleterious consequences of excessive adiposity have great clinical importance. In recent years, increasing interest has been raised regarding the impact of body fat composition or distribution to alterations in cardiac structure and function[1,2]. A number of studies have shown that measures of central adiposity such as waist circumference are superior to measures of global adiposity such as weight and body mass index (BMI) in assessing the risk of cardiovascular disease[3](CVD) and all-cause and cardiovascular-specific mortality[4]. Central obesity is also independently associated with left ventricular (LV) diastolic dysfunction[5-7].

Pathophysiology of adipocyte-mediated systemic inflammation

Obesity is a state of chronic systemic inflammation resulting from interactions between adipocytes and the macrophages recruited to adipose tissue. As a hallmark of obesity, adipose tissue inflammation may play as a central factor in mediating subsequent metabolic derangements and clinical disorders[8-10]. More and more data had indicated that the regulation of immune cells infiltration and pro-inflammatory cytokines production as a consequence of altered inflammatory signaling by macrophages may modulate adipose tissue inflammation to a degree[11,12], which in part helps to explain the transition of excessive visceral adiposity deposition to several unfavorable biological effects. In this regard, more recent studies had demonstrated that M1-type macrophages may serve as a link to lipodystrophy by their infiltrate into adipose tissues of obese individuals via MCP1, where they are activated by saturated fatty acids, leading to low-grade inflammation by producing various pro-inflammatory cytokines[13,14]. Instead, the differentiation of tissue-resident M2-like macrophages by trib1 gene in the bone marrow may play a major role in maintaining the homeostasis of adipose and the hepatic tissue in response to IL-4 and IL-13 from eosinophils via a PPAR-γ- and PPAR-δ-dependent mechanisms, respectively[15-17]. A recent report also revealed that Trib1 gene may play as critical role in the differentiation of M2-like macrophage and several other forms of circulating white blood cells via the ubiquitin-binding domain, another form of macrophage other than M1, had a central role in regulating insulin resistance, triglyceride level, as well as mediating pro-inflammatory cytokines levels[18].

In this regard, through measurement of excessive visceral adipose tissue surrounding vital organs, investigators have demonstrated that visceral fat is biologically active and could be a key mediator of various metabolic derangements, systemic inflammation process[19] with cytokine effects leading to adverse cardiovascular events or progressive heart failure[20,21]. Most studies have used high-sensitivity C-reactive protein (hs-CRP) to represent the extent of vascular and systemic inflammation response[22]. It has also been widely advocated as a novel risk factor of CVD[23]. For instance, the JUPITER trial demonstrated that statin can reduce CVD incidence in overweight subjects with normal lipid profile and elevated Hs-CRP levels[24]. One interpretation of the study results was that Hs-CRP is not only an inflammatory marker, but also plays a direct role in the pathogenesis of atherosclerosis and thrombosis[25].

Effects of epicardial fat on cardiac structural remodeling and dysfunction

Our team has reported previously that epicardial fat was independently associated with metabolic derangements and systemic inflammation[26,27]. The specific effects of epicardial fat on LV structural remodeling in terms of greater concentricity and functional disturbances that may be mediated by various mechanisms including mechanical, paracrine, and systemic processes have been suggested [28,29]. Furthermore, direct compression of the heart by this enveloping fat deposit may cause impaired LV diastolic filling, leading to atrial remodeling and enlargement[30].

Importantly, the association between regional adiposity and cardiac structural or functional remodeling is not limited to the ventricle, and may also involve left atrium (LA) which was evidenced by the Framingham Heart Study[31]. In that study, the authors reported their findings in that larger pericardial fat volume was independently associated with greater LA size in men, with such relationship remained significant after adjustment for body weight and total visceral fat volume. The fact that LA enlargement may be independent of conventional anthropometrics suggests a possible biological role for local pericardial fat on LA remodeling beyond systemic obesity. LA enlargement has long been regarded as one of the strongest predictors for the development of atrial fibrillation (AF). Pericardial fat has also been observed to be independently associated with AF incidence beyond traditional risk factors, including LA size[32,33]. It may also have predictive value for recurrent paroxysmal AF after ablation[34]. This further provided insights about the possible role of pericardial adipose burden in the pathophysiological link to AF development.

The differential effects of total visceral fat, epicardial and intrathoracic fat on the cardiovascular system have been compared in previous literature, especially in the Framingham Heart Study[35,36]. This may be attributed to their different origins of blood supply. Abdominal visceral fat shares the same circulation with the hepatic portal system, so it may be associated with hepatocytic insulin resistance and systemic effects on atherosclerosis[37,38]. On the other hand, the inflammatory effect of epicardial fat was suggested to be more local than systemic, owing to its proximity to the surrounding coronary arteries and myocardium[35,39,40]. As for intrathoracic periaortic or mediastinal fat, their association with CVD is weak because of small volume and lack of anatomical proximity.

Biochemical and genetic mechanisms

Interestingly, the exact pathophysiological role of epicardial adiposity remains controversial so far[40-43]. As a potential source of pro-atherogenic adipokines and inflammatory mediators[44], epicardial fat may exert its toxic effect by either local secretion or systemic inflammation[45]. Due to its proximity to the myocardium and the same coronary blood supply, epicardial fat may have stronger correlations with coronary vasculopathy[46], cardiac structure and function than other measures of adiposity, such as total visceral fat or subcutaneous fat tissue[47].

The linear relationship between intra-myocardial lipids and typical adipose tissue locations[48] in subjects with excessive fat depots remains to be clarified. Indeed, certain kinds of myocardial steatosis and dysfunction in a more extreme clinical scenario, namely cardiac lipotoxicity[49,50], may happen with long-term exposure to circulating free fatty acid (FFA) level in subjects with diabetes[51,52], leading to obviously increased intra-myocardial triglyceride (TG) deposition and impaired cardiac function[53]. Re-esterization to TG formation rather than classical oxidation of the over-influx of cardiac FFA has thus been proposed as the main mechanism underlying, in part may be further driven and aggravated by FFA high turn-over process generating potentially noxious intermediate metabolites (eg. ceramide), causing mitochondrial and myocardial functional decline[54] (Figure 1).

Recent large scale genome-wide association studies have identified genomic loci for indices of body fat distribution that are independent of BMI[55-57], further suggesting the possible existence of unique genetic variants associated with pericardial fat independent of other body fat depots. In one large meta-analysis[58] of the Framingham Heart Study (FHS) and the Multi-Ethnic Study of Atherosclerosis (MESA), through single nucleotide polymorphism (SNP) genotyping in more than 5000 individuals, a genome-wide significant signal was identified near TRIB2 gene. This SNP was not associated with visceral fat or body mass index. TRIB2 gene expression was also observed in the pericardial fat of mice. This association was limited to pericardial fat, not measures of generalized or visceral adiposity. These findings suggest that unique genetic signatures may be specifically linked to different ectopic fat depots.

The obesity paradox

The paradoxical protective effect of central obesity has been widely explored in current literature[59-61]. Under normal physiologic conditions, epicardial fat may act as a local energy reservoir or a buffer against excessive free fatty acids (FFA) to protect the myocardium from their toxic effects[62]. On the other hand, it can also release energy rapidly in the form of FFAs to meet increased myocardial energy demands, particularly during myocardial ischemia[63]. Besides energy storage, the epicardial adipose tissue is also an active source of circulating adipokines (eg: interleukins, tumor necrosis factors) that can profoundly affect energy metabolism as well as systemic inflammation[45-64]. Although these inflammatory reactions are mostly detrimental to the cardiovascular system, some positive effects may exist, such as the angiogenesis of collateral circulation in patients with coronary artery disease[45]. This implies more evidence that such regional adipose tissues can be beneficial by preserving myocardial energy under certain circumstances.


In conclusion, we reviewed the adverse effects of systemic obesity and regional adipose tissue burden on cardiac function from various aspects, including biochemical components, mechanics and genetic issues. Accumulating evidence has supported the hypothesis that epicardial and pericardial fat should be regarded as an independent novel risk factor for cardiovascular disease. The concept that it is a key factor in modulating the process of cardiac structural and functional derangements is becoming more and more widely recognized, and further research on pathophysiologic signaling, pathways and potential therapeutic interventions are warrant in the era of high prevalence of obesity and related metabolic abnormalities.


There are no conflicts of interest with regard to the present study.


1 Lauer MS, Anderson KM, Kannel WB, Levy D. The impact of obesity on left ventricular mass and geometry. The Framingham Heart Study. JAMA 1991; 266: 231-236

2 Gates PE, Gentile CL, Seals DR, Christou DD. Adiposity contributes to differences in left ventricular structure and diastolic function with age in healthy men. J Clin Endocrinol Metab 2003; 88: 4884-4890

3 Huxley R, Mendis S, Zheleznyakov E, Reddy S, Chan J. Body mass index, waist circumference and waist:hip ratio as predictors of cardiovascular risk—a review of the literature. Eur J Clin Nutr 2010; 64: 16-22

4 Pischon T, Boeing H, Hoffmann K, Bergmann M, Schulze MB, Overvad K, et al. General and abdominal adiposity and risk of death in Europe. N Engl J Med 2008; 359: 2105-2120

5 Ammar KA, Redfield MM, Mahoney DW, Johnson M, Jacobsen SJ, Rodeheffer RJ. Central obesity: association with left ventricular dysfunction and mortality in the community. Am Heart J 2008; 156: 975-981

6 Russo C, Jin Z, Homma S, Rundek T, Elkind MS, Sacco RL, Di Tullio MR. Effect of obesity and overweight on left ventricular diastolic function: a community-based study in an elderly cohort. J Am Coll Cardiol 2011; 57: 1368-1374

7 Canepa M, Strait JB, Abramov D, Milaneschi Y, AlGhatrif M, Moni M, Ramachandran R, Najjar SS, Brunelli C, Abraham TP, Lakatta EG, Ferrucci L. Contribution of central adiposity to left ventricular diastolic function (from the Baltimore Longitudinal Study of Aging). Am J Cardiol 2012; 109: 1171-1178

8 Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AWJ. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003; 112: 1796-1808

9 Lumeng CN, DeYoung SM, Bodzin JL, Saltiel AR. Increased inflammatory properties of adipose tissue macrophages recruited during dietinduced obesity. Diabetes 2007; 56: 16-23

10 Huo Y, Guo X, Li H, Wang H, Zhang W, Wang Y, Zhou H, Gao Z, Telang S, Chesney J, Chen YE, Ye J, Chapkin RS, Wu C. Disruption of inducible 6-phosphofructo-2-kinase ameliorates diet-induced adiposity but exacerbates systemic insulin resistance and adipose tissue inflammatory response. J Biol Chem 2010; 285: 3713-3721

11 Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 2003; 112: 1821-1830

12 Arkan MC, Hevener AL, Greten FR, Maeda S, Li Z-W, 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

13 Wellen KE, Hotamisligil GS. Obesity-induced inflammatory changes in adipose tissue. J Clin Invest 2003; 112: 1785-1788

14 Hotamisligil GS. Inflammation and metabolic disorders. Nature 2006; 444: 860-867

15 Odegaard JI, Ricardo-Gonzalez RR, Goforth MH, Morel CR, Subramanian V, Mukundan L, Red Eagle A, Vats D, Brombacher F, Ferrante AW, Chawla A. Macrophage-specific PPARγ controls alternative activation and improves insulin resistance. Nature 2007; 447: 1116-1120

16 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

17 Odegaard JI, Ricardo-Gonzalez RR, Red Eagle A, Vats D, Morel CR, Goforth MH, Subramanian V, Mukundan L, Ferrante AW, Chawla A. Alternative M2 activation of Kupffer cells by PPARδ ameliorates obesity-induced insulin resistance. Cell Metab 2008; 7: 496-507

18 Satoh T, Kidoya H, Naito H, Yamamoto M, Takemura N, Nakagawa K, Yoshioka Y, Morii E, Takakura N, Takeuchi O, Akira S. Critical role of Trib1 in differentiation of tissue-resident M2-like macrophages. Nature 2013; 495: 524-528

19 Langenberg C, Bergstrom J, Scheidt-Nave C, Pfeilschifter J, Barrett-Connor E. Cardiovascular death and the metabolic syndrome: role of adiposity-signaling hormones and inflammatory markers. Diabetes Care 2006; 29: 1363-1369

20 Janssen I, Heymsfield SB, Allison DB, Kotler DP, Ross R. Body mass index and waist circumference independently contribute to the prediction of nonabdominal, abdominal subcutaneous, and visceral fat. Am J Clin Nutr 2002; 75: 683-688

21 Kardys I, Knetsch AM, Bleumink GS, Deckers JW, Hofman A, Stricker BH, Witteman JC. C-reactive protein and risk of heart failure. The Rotterdam Study. Am Heart J 2006; 152: 514-520

22 Lai YH, Liu CC, Kuo JY, Hung TC, Wu YJ, Yeh HI, Bulwer BE, Hung CL. Independent effects of body fat and inflammatory markers on ventricular geometry, midwall function, and atrial remodeling. Clin Cardiol 2014; 37: 172-177

23 Libby P, Ridker PM. Novel inflammatory markers of coronary risk: theory versus practice. Circulation 1999; 100: 1148-1150

24 Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ; JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008; 359: 2195-2207

25 Danenberg HD, Szalai AJ, Swaminathan RV, Peng L, Chen Z, Seifert P, Fay WP, Simon DI, Edelman ER. Increased thrombosis after arterial injury in human C-reactive proteintransgenic mice. Circulation 2003; 108: 512-515

26 Lai YH, Yun CH, Yang FS, Liu CC, Wu YJ, Kuo JY, Yeh HI, Lin TY, Bezerra HG, Shih SC, Tsai CH, Hung CL. Epicardial adipose tissue relating to anthropometrics, metabolic derangements and fatty liver disease independently contributes to serum high-sensitivity C-reactive protein beyond body fat composition: a study validated with computed tomography. J Am Soc Echocardiogr 2012; 25: 234-241

27 Yun CH, Lin TY, Wu YJ, Liu CC, Kuo JY, Yeh HI, Yang FS, Chen SC, Hou CJ, Bezerra HG, Hung CL, Cury RC. Pericardial and thoracic peri-aortic adipose tissues contribute to systemic inflammation and calcified coronary atherosclerosis independent of body fat composition, anthropometric measures and traditional cardiovascular risks. Eur J Radiol 2012; 81: 749-756

28 Sacks HS, Fain JN. Human epicardial adipose tissue: a review. Am Heart J 2007; 153: 907-917

29 Turkbey EB, McClelland RL, Kronmal RA, Burke GL, Bild DE, Tracy RP, Arai AE, Lima JA, Bluemke DA. The impact of obesity on the left ventricle: the Multi-Ethnic Study of Atherosclerosis (MESA). J Am Coll Cardiol Img 2010; 3: 266-274

30 Iacobellis G, Leonetti F, Singh N, Sharma M. Relationship of epicardial adipose tissue with atrial dimensions and diastolic function in morbidly obese subjects. Int J Cardiol 2007; 115: 272-273

31 Fox CS, Gona P, Hoffmann U, Porter SA, Salton CJ, Massaro JM, Levy D, Larson MG, D'Agostino RB Sr, O'Donnell CJ, Manning WJ. Pericardial fat, intrathoracic fat, and measures of left ventricular structure and function: The Framingham Heart Study. Circulation 2009; 119; 1586-1591

32 Al Chekakie MO, Welles CC, Metoyer R, Ibrahim A, Shapira AR, Cytron J, Santucci P, Wilber DJ, Akar JG. Pericardial fat is independently ssociated with human atrial fibrillation. J Am Coll Cardiol 2010; 56: 784-788.

33 G. Thanassoulis, J.M. Massaro, C.J. O'Donnell, U. Hoffmann, D. Levy, P.T. Ellinor, T.J. Wang, R.B. Schnabel, R.S. Vasan, C.S. Fox, E.J. Benjamin. Pericardial fat is associated with prevalent atrial fibrillation: the Framingham Heart Study. Circ Arrhythmia Electrophysiol 2010; 3: 345-350

34 Chao TF, Hung CL, Tsao HM, Lin YJ, Yun CH, Lai YH, Chang SL, Lo LW, Hu YF, Tuan TC, Chang HY, Kuo JY, Yeh HI, Wu TJ, Hsieh MH, Yu WC, Chen SA. Epicardial adipose tissue thickness and ablation outcome of atrial fibrillation. PLoS One 2013; 8: e74926

35 Rosito GA, Massaro JM, Hoffmann U, Ruberg FL, Mahabadi AA, Vasan RS, O'Donnell CJ, Fox CS. Pericardial fat, visceral abdominal fat, cardiovascular disease risk factors, and vascular calcification in a community-based sample: the Framingham Heart Study. Circulation 2008; 117: 605-613

36 Mahabadi AA, Massaro JM, Rosito GA, Levy D, Murabito JM, Wolf PA, O'Donnell CJ, Fox CS, Hoffmann U. Association of pericardial fat, intrathoracic fat, and visceral abdominal fat with cardiovascular disease burden: the Framingham Heart Study. Eur Heart J 2009; 30: 850-856

37 Fox CS, Massaro JM, Hoffmann U, Pou KM, Maurovich-Horvat P, Liu CY, Vasan RS, Murabito JM, Meigs JB, Cupples LA, D’Agostino RB Sr, O’Donnell CJ. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation 2007; 116: 39-48

38 Pou KM, Massaro JM, Hoffmann U, Vasan RS, Maurovich-Horvat P, Larson MG, Keaney JF Jr, 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

39 Taguchi R, Takasu J, Itani Y, Yamamoto R, Yokoyama K, Watanabe S, Masuda Y. Pericardial fat accumulation in men as a risk factor for coronary artery disease. Atherosclerosis 2001; 157: 203-209

40 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

41 Sacks HS, Fain JN. Human epicardial fat: what is new and what is missing? Clin Exp Pharmacol Physiol 2011; 38: 879-887

42 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

43 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 vitro. Int J Obes 1990; 14: 1013-1022

44 Spiroglou SG, Kostopoulos CG, Varakis JN, Papadaki HH. Adipokines in periaortic and epicardial adipose tissue: differential expression and relation to atherosclerosis. J Atheroscler Thromb 2010; 17: 115-130

45 Mazurek T, Zhang L, Zalewski A, Mannion JD, Diehl JT, Arafat H, Sarov-Blat L, O'Brien S, Keiper EA, Johnson AG, Martin J, Goldstein BJ, Shi Y. Human epicardial adipose tissue is a source of inflammatory mediators. Circulation 2003; 108: 2460-2466

46 Wang CP, Hsu HL, Hung WC, Yu TH, Chen YH, Chiu CA, Lu LF, Chung FM, Shin SJ, Lee YJ. Increased epicardial adipose tissue (EAT) volume in type 2 diabetes mellitus and association with metabolic syndrome and severity of coronary atherosclerosis. Clin Endocrinol 2009; 70: 876-882

47 Iacobellis G, Pond CM, Sharma AM. Different “weight” of cardiac and general adiposity in predicting left ventricle morphology. Obesity (Silver Spring) 2006; 14: 1679-1684

48 Zhou YT, Grayburn P, Karim A, Shimabukuro M, Higa M, Baetens D, Orci L, Unger RH. Lipotoxic heart disease in obese rats: implications for human obesity. Proc Natl Acad Sci USA 2000; 97: 1784-1789

49 Malavazos AE, Di Leo G, Secchi F, Lupo EN, Dogliotti G, Coman C, Morricone L, Corsi MM, Sardanelli F, Iacobellis G. Relation of echocardiographic epicardial fat thickness and myocardial fat. Am J Cardiol 2010; 105: 1831-1835

50 Kankaanpää M, Lehto HR, Pärkkä JP, Komu M, 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

51 McGavock JM, Lingvay I, Zib I, Tillery T, Salas N, Unger R, Levine BD, Raskin P, Victor RG, Szczepaniak LS. Cardiac steatosis in diabetes mellitus: a 1H-magnetic resonance spectroscopy study. Circulation 2007; 116: 1170-1175

52 Rijzewijk LJ, van der Meer RW, Smit JW, Diamant M, Bax JJ, Hammer S, Romijn JA, de Roos A, Lamb HJ. Myocardial steatosis is an independent predictor of diastolic dysfunction in type 2 diabetes mellitus. J Am Coll Cardiol 2008; 52: 1793-1799

53 Gastaldelli A, Morales MA, Marraccini P, Sicari R. The role of cardiac fat in insulin resistance. Curr Opin Clin Nutr Metab Care 2012; 15: 523-528

54 Christoffersen C, Bollano E, Lindegaard ML, Bartels ED, Goetze JP, Andersen CB, Nielsen LB. Cardiac lipid accumulation associated with diastolic dysfunction in obese mice. Endocrinology 2003; 144: 3483-3490.

55 Speliotes EK, Yerges-Armstrong LM, Wu J, Hernaez R, Kim LJ, et al; MAGIC Investigators, Voight BF, Carr JJ, Feitosa MF, Harris TB, Fox CS, Smith AV, Kao WH, Hirschhorn JN, Borecki IB; GOLD Consortium. Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits. PLoS Genet 2011; 7: e1001324

56 Heid IM, Jackson AU, Randall JC, Winkler TW, Qi L, et al. Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. Nat Genet 2010; 42: 949-960

57 Kilpelainen TO, Zillikens MC, Stancakova A, Finucane FM, Ried JS, et al. Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile. Nat Genet 2011; 43: 753-760

58 Fox CS, White CC, Lohman K, Heard-Costa N, Cohen P, Zhang Y, Johnson AD, Emilsson V, Liu CT, Chen YD, Taylor KD, Allison M, Budoff M; CARDIoGRAM Consortium, Rotter JI, Carr JJ, Hoffmann U, Ding J, Cupples LA, Liu Y. Genome-wide association of pericardial fat identifies a unique locus for ectopic fat. PLoS Genet 2012; 8: e1002705

59 Bechlioulis A, Vakalis K, Naka KK, Bourantas CV, Papamichael ND, Kotsia A, Tzimas T, Pappas K, Katsouras CS, Michalis LK. Paradoxical protective effect of central obesity in patients with suspected stable coronary artery disease. Obesity (Silver Spring) 2013; 21: E314-321

60 Habbu A, Lakkis NM, Dokainish H. The obesity paradox: fact or fiction? Am J Cardiol 2006; 98: 944-948

61 Hainer V, Aldhoon-Hainerová I. Obesity paradox does exist. Diabetes Care 2013; 36 Suppl 2: S276-281

62 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

63 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

62 Spiroglou SG, Kostopoulos CG, Varakis JN, Papadaki HH. Adipokines in periaortic and epicardial adipose tissue: differential expression and relation to atherosclerosis. J Atheroscler Thromb 2010; 17: 115-130

Peer reviewers: Catarina Margarida da Silva Vasques, PhD, Associate Professor in the Department of Sport Science and Physical Education, Polytechnic Institute of Bragança,Campus de Santa Apolónia – Apartado 1038 5301-854 Bragança, Portugal; Adriana Georgescu, PhD, Principal Investigator, Department of Pathophysiology and Pharmacology, Institute of Cellular Biology and Pathology Nicolae Simionescu, 8 B.P. Hasdeu Street, Bucharest, 050568, Romania.


  • There are currently no refbacks.

Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.