Browning Epicardial Adipose Tissue: Friend or Foe?

Abstract

The epicardial adipose tissue (EAT) is the visceral fat depot of the heart which is highly plastic and in direct contact with myocardium and coronary arteries. Because of its singular proximity with the myocardium, the adipokines and pro-inflammatory molecules secreted by this tissue may directly affect the metabolism of the heart and coronary arteries. Its accumulation, measured by recent new non-invasive imaging modalities, has been prospectively associated with the onset and progression of coronary artery disease (CAD) and atrial fibrillation in humans. Recent studies have shown that EAT exhibits beige fat-like features, and express uncoupling protein 1 (UCP-1) at both mRNA and protein levels. However, this thermogenic potential could be lost with age, obesity and CAD. Here we provide an overview of the physiological and pathophysiological relevance of EAT and further discuss whether its thermogenic properties may serve as a target for obesity therapeutic management with a specific focus on the role of immune cells in this beiging phenomenon.

Keywords: adipose tissue; beiging; browning; coronary artery disease; ectopic fat; epicardial adipose tissue; heart; immune cells; innate lymphoid cells.

Figure 1

The crosstalk between epicardial adipose tissue and the cardiovascular system. A local crosstalk takes place between EAT (epicardial adipocytes and other EAT composing cells) and the cardiovascular system (e.g., myocardium and coronary arteries). Physiological and pathophysiological signals such as cytokines, adipokines or fibrokines can be released from EAT to cardiomyocytes (and from myocardium to EAT) or coronary artery endothelial cells (grey arrows). Theses cytokines can have protective and/or beneficial effects (green) or harmful effects (red). Other molecules’ effects are still not well established or are controversial (black).

Figure 2

White, Beige and Brown adipocyte markers in Human and Mouse. We summed up here genes reported in the literature as markers of white (WAT), beige and brown adipose tissues (BAT) and shared by beige and WAT or beige and BAT in humans (a) and mice (b).

Figure 3

Potential factors involved in the EAT browning. Putative mechanisms based on work realized in adipose tissue in general. Environmental factors such as cold exposure, physical exercise, pharmacological treatments and dietary are implicated in browning of white adipocytes but the mechanisms underlying are not yet well established (dotted arrows). Inter-cellular communication factors involving cytokines/chemokines (purple), myokines (blue), hormones (red) and miRs (green) are known to be involved in WAT browning. EVs: extracellular vesicles; β-Ara: β-adrenergic receptor agonists; GLP1-Ra: GLP1- receptor agonists; NPa natriuretic peptide agonists; METRNL: Meteorin Like; MetEnk: methionine enkephalin, NE: norepinephrine, FGF21: fibroblast growth factor 21; FGFR1: FGF receptor 1; KLB: coreceptor Beta-klotho.