Extracellular Vesicles in Adipose Tissue Communication with the Healthy and Pathological Heart

Abstract

Adipose tissue and its diverse cell types constitute one of the largest endocrine organs. With multiple depot locations, adipose tissue plays an important regulatory role through paracrine and endocrine communication, particularly through the secretion of a wide range of bioactive molecules, such as nucleic acids, proteins, lipids or adipocytokines. Over the past several years, research has uncovered a myriad of interorgan communication signals mediated by small lipid-derived nanovesicles known as extracellular vesicles (EVs), in which secreted bioactive molecules are stably transported as cargo molecules and delivered to adjacent cells or remote organs. EVs constitute an essential part of the human adipose secretome, and there is a growing body of evidence showing the crucial implications of adipose-derived EVs in the regulation of heart function and its adaptative capacity. The adipose tissue modifications and dysfunction observed in obesity and aging tremendously affect the adipose-EV secretome, with important consequences for the myocardium. The present review presents a comprehensive analysis of the findings in this novel area of research, reports the key roles played by adipose-derived EVs in interorgan cross-talk with the heart and discusses their implications in physiological and pathological conditions affecting adipose tissue and/or the heart (pressure overload, ischemia, diabetic cardiomyopathy, etc.).

Keywords: adipocytes; adipose tissue; cardiac physiology; endocrine communication; exosomes; extracellular vesicles; heart disease; heart failure; ischemia; obesity.

Figure 1

Schematic representation of white, beige and brown adipocytes and their thermogenesis mechanisms, including activation of the lipolysis of lipid droplets via beta-adrenergic stimulation, the uncoupling of mitochondrial respiration via uncoupling protein 1 (UCP1) and futile Ca²⁺ cycling via the endoplasmic reticulum Ca²⁺ ATPase SERCA. In white adipocytes, beta-adrenergic stimulation induces lipolysis, leading to non-esterified free fatty acid release from their unique lipid droplets in the absence of thermogenesis.

Figure 2

Schematic representation of the impact of adipose-derived EVs on heart function in healthy and pathological adipose tissues as seen in the context of obesity.