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Review
. 2022 Sep;19(9):593-606.
doi: 10.1038/s41569-022-00679-9. Epub 2022 Mar 16.

Epicardial adipose tissue in contemporary cardiology

Affiliations
Review

Epicardial adipose tissue in contemporary cardiology

Gianluca Iacobellis. Nat Rev Cardiol. 2022 Sep.

Abstract

Interest in epicardial adipose tissue (EAT) is growing rapidly, and research in this area appeals to a broad, multidisciplinary audience. EAT is unique in its anatomy and unobstructed proximity to the heart and has a transcriptome and secretome very different from that of other fat depots. EAT has physiological and pathological properties that vary depending on its location. It can be highly protective for the adjacent myocardium through dynamic brown fat-like thermogenic function and harmful via paracrine or vasocrine secretion of pro-inflammatory and profibrotic cytokines. EAT is a modifiable risk factor that can be assessed with traditional and novel imaging techniques. Coronary and left atrial EAT are involved in the pathogenesis of coronary artery disease and atrial fibrillation, respectively, and it also contributes to the development and progression of heart failure. In addition, EAT might have a role in coronavirus disease 2019 (COVID-19)-related cardiac syndrome. EAT is a reliable potential therapeutic target for drugs with cardiovascular benefits such as glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter 2 inhibitors. This Review provides a comprehensive and up-to-date overview of the role of EAT in cardiovascular disease and highlights the translational nature of EAT research and its applications in contemporary cardiology.

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Conflict of interest statement

The author declares no competing interests.

Figures

Fig. 1
Fig. 1. EAT changes with age and in pathological conditions.
In the neonate and early years of life, epicardial adipose tissue (EAT) is morphologically and functionally similar to brown adipose tissue. Under physiological conditions, the brown fat-like properties of EAT rapidly decrease with age, from childhood to adulthood. However, EAT maintains cardioprotective functions such as providing a source of energy and heat to the heart. In pathological conditions, such as coronary artery disease, diabetes mellitus, heart failure and atrial fibrillation, EAT becomes pro-atherogenic and pro-arrhythmogenic. In patients with advanced or end-stage organ disease, such as cardiac diseases, and in elderly individuals, the thermogenic function of EAT can be further decreased, with reciprocal increases in the expression of genes encoding profibrotic and pro-apoptotic factors.
Fig. 2
Fig. 2. Role of regional EAT depots on coronary artery disease and atrial fibrillation.
The epicardial adipose tissue (EAT) is distributed as localized depots lying between the myocardium and the visceral layer of the pericardium. EAT can infiltrate the left atrium (left atrial EAT) and surround the coronary arteries (coronary EAT). By contrast, pericardial adipose tissue (PAT) is located more externally, within the visceral and parietal layers of the pericardium. EAT contributes to the development and progression of coronary artery disease and atrial fibrillation through complex and multifactorial pathways. The regional distribution of EAT has an important role because each EAT depot is anatomically, genetically and functionally different. a | Left atrial EAT has a high expression of genes encoding pro-arrhythmogenic factors. Left atrial EAT can contribute to atrial fibrillation through the local secretion of profibrotic factors (matrix metalloproteinases (MMPs), transforming growth factor-β1 (TGFβ1) and TGFβ2, connective tissue growth factor (cTGF) and activin A) and inflammatory factors (IL-6 and tumour necrosis factor (TNF)) as well as free fatty acid (FFA) infiltration and increased autonomic control via ganglionated plexi. b | The coronary EAT has a high expression of genes encoding pro-inflammatory adipokines and factors regulating glucose and lipid metabolism. Coronary EAT can influence the development and progression of coronary artery disease through increased infiltration of pro-inflammatory M1 macrophages from EAT into the adjacent myocardium, the paracrine or vasocrine release of several pro-inflammatory cytokines (CCL2, IL-6 and TNF) and adipokines (chemerin, intelectin 1 (also known as omentin 1), resistin and serglycin), and the activation of innate immune response factors such as JUN N-terminal kinase (JNK), nuclear factor-κB (NF-κB) and Toll-like receptors (TLRs). Upregulation of signalling via advanced glycation end products (AGE) binding to their receptor RAGE in EAT can contribute to the oxidative stress and endothelial damage associated with coronary atherosclerosis in patients with diabetes mellitus. The excessive influx of FFAs from EAT into the coronary arteries is mediated by enzymes such as group II secretory phospholipase A2 (sPLA2-II) and adipocyte fatty acid-binding protein (also known as FABP4). GLUT4, glucose transporter type 4.
Fig. 3
Fig. 3. Atherogenic effects of coronary EAT on the coronary artery.
In patients with coronary artery disease, coronary epicardial adipose tissue (EAT) has a dense inflammatory infiltrate with a high prevalence of pro-inflammatory M1 macrophages. Coronary EAT secretes pro-inflammatory cytokines (such as CCL2, IL-6 and tumour necrosis factor (TNF)) and adipokines (such as chemerin, intelectin 1 (also known as omentin 1), resistin and serglycin) into the coronary lumen, thereby contributing to systemic inflammation. Coronary EAT inflammation also contributes locally to coronary atherosclerotic plaque inflammation. The upregulation in the coronary EAT of innate immune response signalling, such as JUN N-terminal kinase (JNK), nuclear factor-κB (NF-κB) and Toll-like receptor (TLR) signalling, can also induce the secretion of inflammatory mediators from the coronary EAT. The excessive influx of free fatty acids (FFAs) mediated by group II secretory phospholipase A2 (sPLA2-II) and adipocyte fatty acid-binding protein (also known as FABP4) from epicardial adipocytes might infiltrate the adventitia and contribute to the lipid build-up in coronary artery atherosclerotic plaques. The co-occurrence of coronary artery disease with chronic hyperglycaemia can upregulate signalling via advanced glycation end products (AGE) binding to their receptor RAGE and reduce levels of glucose transporter type 4 (GLUT4), thereby contributing to oxidative stress and endothelial cell damage.
Fig. 4
Fig. 4. Arrhythmogenic effects of left atrial EAT on the cardiomyocyte.
Given the anatomical contiguity of left atrial epicardial adipose tissue (EAT) with the adjacent left atrium, profibrotic factors (such as activin A, connective tissue growth factor (cTGF), matrix metalloproteinases (MMPs), and transforming growth factor-β1 (TGFβ1) and TGFβ2) released by EAT, via secretion or through extracellular vesicles (EVs), can cause atrial myocardial fibrosis. Left atrial EAT can also contribute to atrial fibrillation through the local secretion of pro-inflammatory factors such as IL-6 and tumour necrosis factor (TNF). Excessive influx of free fatty acids (FFAs) from the left atrial EAT affects the continuity of cardiomyocytes, causing ‘zig-zag’ conduction and facilitating the development of re-entrant circuits. The increased activity of the ganglionated plexi in EAT can increase the autonomic effects of atrial cardiomyocytes and prolong the action potential duration. ECM, extracellular matrix.
Fig. 5
Fig. 5. Role of EAT in heart failure.
Epicardial adipose tissue (EAT) can affect heart function in the setting of heart failure via inflammation, fibrosis and neural dysregulation as observed in coronary artery disease and atrial fibrillation. However, several specific mechanisms link EAT with heart failure. The EAT proteome can contribute to the pathogenesis of heart failure through the paracrine secretion of profibrotic factors, such as α1-antichymotrypsin (ACT; also known as serpin A3) and matrix metalloproteinase 14 (MMP14), inflammatory markers, such as p53, and free fatty acids (FFAs). Large and fibrotic EAT can also exert mechanical effects on both diastolic and systolic function. EAT can also be involved in the pathogenesis of heart failure through neurohormonal mechanisms. The increased catecholamine biosynthetic activity of EAT can increase noradrenaline accumulation in the myocardium and worsen systolic performance. ECM, extracellular matrix.
Fig. 6
Fig. 6. Targeting EAT with GLP1R agonists and SGLT2 inhibitors.
Potential beneficial cardiometabolic effects of sodium–glucose co-transporter 2 (SGLT2) inhibitor and glucagon-like peptide 1 receptor (GLP1R) agonist therapies beyond their glycaemic and haemodynamic effects. SGLT2 inhibitors and GLP1R agonists can target both left atrial epicardial adipose tissue (EAT) and coronary EAT for the treatment and prevention of atrial fibrillation (part a) and coronary artery disease (part b), respectively. Both SGLT2 inhibitors and GLP1R agonists can reduce EAT inflammation and increase free fatty acid (FFA) oxidation as fuel for the myocardium, and GLP1R agonists induce fat browning (white to brown fat differentiation and pre-adipocyte differentiation, leading to improved myocardial insulin sensitivity), all of which improve myocardial metabolism. SGLT2 inhibitors can induce sympatholytic and lipolytic effects in EAT to increase ketogenesis and reduce oxygen consumption in the setting of heart failure.

References

    1. Iacobellis G, et al. Epicardial fat from echocardiography: a new method for visceral adipose tissue prediction. Obes. Res. 2003;11:304–310. doi: 10.1038/oby.2003.45. - DOI - PubMed
    1. Iacobellis G, 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;388:5163–5168. doi: 10.1210/jc.2003-030698. - DOI - PubMed
    1. 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. doi: 10.1038/ncpcardio0319. - DOI - PubMed
    1. McAninch EA, et al. Epicardial adipose tissue has a unique transcriptome modified in severe coronary artery disease. Obesity. 2015;23:1267–1278. doi: 10.1002/oby.21059. - DOI - PMC - PubMed
    1. Iacobellis G. Local and systemic effects of the multifaceted epicardial adipose tissue depot. Nat. Rev. Endocrinol. 2015;11:363–371. doi: 10.1038/nrendo.2015.58. - DOI - PubMed