Key result
Semaglutide reduces epicardial fat paracrine protein secretion and modulates KCa1.1 and Nav1.5 ion channel expression.
Why the study?
There was a need to identify the differential proteins released by adipose and non-adipose epicardial layers and determine how their paracrine effects on myocardium are modulated by semaglutide.
Does semaglutide modulate the paracrine activity and protein secretion profiles of adipose and non-adipose layers of the epicardium?
Does semaglutide modulate the paracrine activity and protein secretion profiles of adipose and non-adipose layers of the epicardium?
Semaglutide modulates the paracrine activity of epicardial adipose tissue, primarily affecting the adipose layer to alter protein secretion and cardiomyocyte ion channel expression.
Semaglutide alters epicardial fat paracrine signaling ex vivo; hypothesis-generating for cardiac effects beyond glycemic control.
Background Alongside being an energy source, epicardial adipose tissue (EAT) shows paracrine effects over myocardium. This fat has two main layers according to adiposity presence. Thus, while fatty acid binding protein 4 (FABP4) levels, mainly produced by adipocytes, is a detrimental marker, omentin, mainly produced by non-adipose layer, is a protective protein. The recent long-acting GLP1 receptor agonist (GLP1ra), semaglutide, has demonstrated its ability to reduce epicardial fat volume with cardiac benefits. However, there is a scientific need to identify the main differential released proteins according to adiposity presence and drugs regulation. Purpose We aimed to characterize the differential paracrine activity of epicardium layers, their effects over myocardium, and its modulation by semaglutide, using hiPSC-atrial cardiomyocytes. Methods This study was approved by the Galician Research Ethics Committee. Epicardial fat biopsies were obtained from 8 patients who underwent open heart surgery. The tissues were split into two main layers depending on adipocytes presence and treated or not with 1 nM semaglutide for 72 hours. Later the secreted proteins were studied by proteomics (Triple-TOF), mRNA levels on tissue were studied by RT-qPCR, conditioned medium over hiPSC-atrial cardiomyocytes were used for paracrine studies, considering in ion channel expression levels by RT-qPCR. Results Adipose and non-adipose layer had different released protein profiles. The adipose layer showed mainly proteins regarding fatty acid metabolism whereas non-adipose layer demonstrated mostly structural organization proteins. Semaglutide treatment reduces the secretion of the adipose layer and increases those of non-adipose layer. Conditioned medium from adipose layer over cardiomyocytes showed an upregulation of the expression levels of KCa1.1. and Nav1.5. which were modulated after semaglutide treatment. Conclusions Adipose and non-adipose layers from the epicardium have different protein profiles and differential paracrine activities over cardiomyocytes, which are both modified by semaglutide. Therefore, we suggest that semaglutide mainly effects on adipose layer of epicardium.
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Basdas et al. (2025) studied this question. Semaglutide vs. Untreated tissue was evaluated on Released protein profiles and ion channel expression. Semaglutide treatment modified the paracrine activity of epicardial fat biopsies, reducing protein secretion from the adipose layer and modulating KCa1.1 and Nav1.5 ion channel expression.
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