Epicardial adipose tissue as a metabolically active visceral fat depot: an emerging target in cardiovascular disease

Background Epicardial adipose tissue (EAT) is a metabolically and endocrinologically active visceral fat depot with unique anatomical proximity to the myocardium, and is increasingly recognized as relevant to cardiovascular health and disease. Its anatomical position, in direct contact with the myocardium and coronary arteries without an intervening fascial barrier, is consistent with paracrine and vasocrine signaling toward adjacent cardiac structures. Objective This review aims to provide a comprehensive analysis of EAT biology, from its physiological roles in lipid homeostasis, mechanical protection, and thermogenesis, to its pathological transformation in the context of obesity, metabolic syndrome, and coronary artery disease. Methods A narrative review was conducted using PubMed/MEDLINE, Scopus, Web of Science, and Embase, focusing on studies published between January 2000 and December 2025. Human data—particularly from prospective cohorts, randomized trials, and meta-analyses—were prioritized over preclinical and in vitro work, with the latter invoked principally to support mechanistic discussion. Detailed search strategy and inclusion criteria are described in the Methods section. Results Under pathological conditions, EAT undergoes structural and functional remodeling characterized by adipocyte hypertrophy, immune cell infiltration, dysregulated adipokine secretion, and a shift from a beige-like thermogenic phenotype to a white, pro-inflammatory depot. These changes promote cardiac fibrosis through activation of fibroblast-to-myofibroblast differentiation via TGF- β /SMAD and biomechanical pathways, contribute to arrhythmogenesis through disruption of connexin-mediated conduction and activation of the adipose-neural axis, and facilitate coronary atherosclerosis through local inflammatory signaling. The renin-angiotensin-aldosterone system plays a critical role in mediating EAT-related inflammation and fibrosis through AT1R-driven pro-inflammatory cascades, while the ACE2/Ang 1–7/MasR axis offers counter-regulatory cardioprotection. Conclusions EAT is an emerging therapeutic target and candidate biomarker in cardiovascular medicine. Echocardiographic thickness and CT/MRI volumetric measurements have shown prognostic associations with adverse cardiovascular events, although standardized cut-off values across imaging modalities and large prospective outcomes trials specifically validating EAT-based risk stratification remain lacking. Strategies that may favorably modulate EAT remodeling, including GLP-1 receptor agonists and conceptual approaches to promote re-browning, represent emerging—but still preliminary—therapeutic directions whose independent cardiovascular benefit requires further investigation.