Assessing the interaction of the UCP system and fatty acids on epicardial adipose tissue mitochondrial respiration

Background Epicardial adipose tissue (EAT) exhibits brown‐like features, including the expression of uncoupling protein 1 (UCP1). EAT interacts dynamically with cardiac cells to modulate local cardiac tissue physiology and metabolic function. No studies have evaluated the impact of UCP1 inhibition on oxidative phosphorylation (OXPHOS) in fresh EAT explants. This study aimed to determine the unique bioenergetic characteristics of fresh EAT explants by comparing it to subcutaneous adipose tissue (SAT). Furthermore, the key impact of UCP1 inhibition on EAT respiration and how this process is influenced by the presence of type 2 diabetes mellitus (DM) or coronary artery disease (CAD), was also evaluated. Methods EAT and SAT biopsies were collected from 205 (151 male and 51 female) study participants, undergoing cardiac surgery. Participants were stratified according to the presence/absence of DM or CAD. Markers of mitochondrial content and bioenergetics were evaluated. Results EAT demonstrated a higher bioenergetic activity compared to SAT, in both nicotinamide adenine dinucleotide (NADH)‐linked and fatty acid oxidation (FAO)‐linked OXPHOS. Importantly, UCP1 inhibition with guanosine 5′‐diphosphate (GDP), flattens the differences between the tissues in the NADH‐linked OXPHOS; in contrast these differences were potentiated in the FAO‐linked OXPHOS. Minor differences in mitochondrial content and respiration were observed when subjects were stratified according to either DM or CAD. Conclusions This study emphasizes the important bioenergetic differences between EAT and SAT, which are crucial in the context of the local cardiomyocyte metabolism, as well as the impact of UCP1 inhibition in EAT. A deeper understanding of the unique characteristics of EAT and its metabolic micro‐environment may provide valuable insights into the cardiovascular disease pathologies.