Abstract
Introduction: An independent link between cardiac adiposity and atrial fibrillation exists. We and others have shown in settings of excess cardiac adiposity, that this adipose exerts a paracrine influence on the myocardium, leading to atrial fibrosis and inter-myocyte conduction slowing. Proteomic analysis has revealed numerous candidate factors released from the adipose that may drive these structural and functional changes. Considerably less is known about potential paracrine actions of epicardial adipose in healthy, lean physiological settings. This study aims to interrogate the proteome of sheep epicardial and subcutaneous adipose tissue paracrine factors as a first step to understand the influence of cardiac adipose tissue in the healthy heart.
Methods: Epicardial (EAT) and subcutaneous (SAT) adipose tissues were collected from healthy 2-year-old female sheep and incubated in protein-free culture media (4hrs, 37°C). The secreted proteins within these ‘conditioned media’ were identified by label-free explorative proteomics using LC-MS/MS instrumentation. Gene ontology analysis (Enrichr/PINE) was applied to the proteomic datasets to profile differences between protein subgroups secreted from the different adipose depots.
Results: A total of 642 proteins were identified within the conditioned media across the two different adipose depots. 137 proteins were identified to be differentially abundant, of which 127 proteins were more abundant in EAT conditioned media and 10 proteins less abundant (vs SAT conditioned media). Of these differentially abundant proteins, PINE analysis predicted an increase in the release from epicardial adipose of proteins associated with tubulin folding, L1CAM interactions, gap junction and lipid metabolism pathways. In contrast, proteins associated with glycolysis/gluconeogenesis were shown to be less abundant.
Conclusions: These data indicate that epicardial adipose likely exerts a paracrine influence in the heart under physiological conditions. A high abundance of tubulin-folding and gap junction-related proteins in EAT conditioned media may indicate greater cell-cell communication between epicardial adipose and other cardiac cells. Current studies are exploring how such communications pathways may influence cardiomyocyte electrophysiology under physiological conditions.