Cardio-Lipotoxicity of Epicardial Adipose Tissue

Abstract

Epicardial adipose tissue is a unique visceral adipose tissue depot that plays a crucial role in myocardial metabolism. Epicardial adipose tissue is a major source of energy and free fatty acids for the adjacent myocardium. However, under pathological conditions, epicardial fat can affect the heart through the excessive and abnormal influx of lipids. The cardio-lipotoxicity of the epicardial adipose tissue is complex and involves different pathways, such as increased inflammation, the infiltration of lipid intermediates such as diacylglycerol and ceramides, mitochondrial dysfunction, and oxidative stress, ultimately leading to cardiomyocyte dysfunction and coronary artery ischemia. These changes can contribute to the pathogenesis of various cardio-metabolic diseases including atrial fibrillation, coronary artery disease, heart failure, and obstructive sleep apnea. Hence, the role of the cardio-lipotoxicity of epicardial fat and its clinical implications are discussed in this review.

Keywords: adipokines; cardiac metabolism; obstructive sleep apnea.

Figure 1

Cardio-lipotoxicity of epicardial adipose tissue. This graphic summarizes the mechanisms underlying the cardio-lipotoxicity of epicardial adipose tissue. The cascade of events hereby described may follow alternate or preferred pathways due to the concurrence of exogenous conditions such as diabetes, obesity, coronary artery disease, or atrial fibrillation. The excessive production and release of free fatty acids through paracrine and vasocrine pathways from epicardial fat into the adjacent myocardium and coronary artery leads to an upregulation of endogenous transcription factors that activate M1 macrophages and increase the production of pro-inflammatory adipokines. The increased inflammatory milieu causes the accumulation and infiltration of lipid intermediates such as diacylglycerol and ceramides within the cardiac cells and coronary lumen that contribute to mitochondrial dysfunction and oxidative stress. The excessive lipid accumulation, due to the saturated capacity to oxidize and utilize the ectopic lipid infiltration, causes coronary plaque build-up and cardiomyocyte fibrosis. Apoptotic changes will ultimately lead to cardiac hypertrophy and/or dilation and coronary artery ischemia.