Epicardial adipose tissue as target of the incretin-based therapies in cardio-metabolic pathologies: a narrative review

Mar 6, 2025Canadian journal of physiology and pharmacology

Incretin-based treatments targeting fat around the heart in heart and metabolism diseases

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Abstract

Epicardial adipose tissue expansion is recognized as an independent risk factor for cardiovascular disease progression.

In physiological conditions, epicardial adipose tissue serves as a protective layer and lipid-storage unit for the heart.
Pathological expansion of epicardial adipose tissue is associated with a shift toward a pro-inflammatory and pro-oxidant state.
Metabolic diseases, such as obesity and diabetes, can exacerbate epicardial adipose tissue expansion and dysregulation.
Increased epicardial adipose tissue is linked to complications like atrial fibrillation and progression toward heart failure.
GLP-1 receptor agonists may offer benefits beyond glycemic control, including weight reduction and cardiac protection in type 2 diabetes patients.

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The epicardial adipose tissue (EAT) serves in physiological conditions as a mechanical and thermal myocardial protective layer, as well as a readily available lipid-storage unit. In pathological conditions, EAT expansion becomes deleterious and is currently recognized as an independent risk factor for the progression of cardiovascular diseases. The EAT phenotypic shift from protective to pro-inflammatory/pro-oxidant is facilitated by the presence of metabolic diseases (obesity, metabolic syndrome, and diabetes), which further increase its expansion and dysregulation, favor the occurrence of complications (mainly atrial fibrillation), and promote progression towards heart failure. Glucagon-like peptide-1 (GLP-1) receptor agonists are novel antidiabetic medications belonging to the incretin class that have demonstrated efficacy beyond glycemic control, in terms of weight reduction and cardiorenal protection in patients with type 2 diabetes mellitus. The GLP-1 receptors and glucose-dependent insulinotropic polypeptide (GIP) receptors are expressed in the human EAT and are targeted by an increasing number of pharmacological agonists, with pleiotropic protective effects on EAT structure and function. Herein we review the literature characterizing the benefits of GLP-1 and GIP receptors activation by single and dual agonists with particular emphasis on their effects on EAT and highlight the role of incretin-based therapy for the management of cardiometabolic pathologies.

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Epicardial adipose tissue as target of the incretin-based therapies in cardio-metabolic pathologies: a narrative review

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