Introduction:
The risk of developing atrial fibrillation (AF), the most common cardiac arrhythmia worldwide, is increased by obesity and other metabolic diseases. Expansion of the fat layer surrounding the heart, epicardial adipose tissue (EAT), is associated with both AF and obesity. Furthermore, EAT has been implicated as an acute trigger for arrhythmogenesis. This study aimed to examine acute mechanisms of EAT-induced arrhythmogenesis, with a focus on the involvement of acute metabolic stress and chronic obesity.
Methods:
Using an in vitro isolated right atrial trabecula model, human trabeculae (n = 21) were exposed to the 24-hour cultured secretome of human EAT from non-obese (BMI < 30 kg/m2; n = 6) or obese (BMI > 30 kg/m2; n = 7) cardiac surgery patients. Arrhythmogenic activity was measured through the development of unstimulated, spontaneous contractions (SCs) by the trabeculae. EAT biopsies were bisected and either left untreated (control) or treated with an acute metabolic stress cocktail of hyperglycaemia, hyperlipidaemia, and hyperinsulinaemia (treatment). To identify differential expression of adipokines induced by the treatment, chronic obesity, or a combination of the two, control and treatment EAT secretome samples from non-obese (n = 7) and obese (n = 7) participants underwent proteomic analysis.
Results:
Neither the control nor treatment secretomes increased the proportion of trabeculae that developed SCs compared to baseline measurements (control: 6/21 & treatment: 5/21 vs. baseline: 8/21, P = 0.70). Similarly, there was no difference in the SC propensity induced by control EAT secretome from non-obese (2/7) and obese participants (4/14, P = 0.56). The control secretome induced a distinctly negative inotropic (Fdev: 2.6 ± 0.7 mN/mm2 vs. baseline 4.0 ± 0.9 mN/mm2, P < 0.0001) and lusitropic (-dF/dtmax: -26.2 ± 6.0 mN/mm2/s vs. baseline −35.1 ± 7.1 mN/mm2/s, P = 0.01) effect, however this was unchanged by either the treatment or obesity. We identified for the first time alterations in adipokine expression in the EAT secretome in obesity, in particular increased expression of calcium-binding S100 proteins (S100A, S100A11, and S100B).
Conclusions:
Human EAT secretome did not affect the arrhythmogenicity of human cardiac muscles, however, it caused negative inotropic and lusitropic effects. No differences were observed in obesity, although the expression of S100 proteins were altered in the EAT secretome. This study thereby provides novel mechanistic insight into the acute paracrine relationship between the EAT secretome and the atrial myocardium in humans, and how this is informed by acute metabolic stress and chronic obesity.
- 9926853271001891
- Investigating the role of the epicardial adipose tissue secretome and obesity in atrial fibrillation
- Kyra T. SinclairIngrid C. Fomison-NurseWillow De JongePhilip J. DavisLisa LimRichard W. BuntonMichael J.A. WilliamsTorsten KleffmanSean CoffeyRegis R. Lamberts
- Medicine (DSM); Physiology; Biochemistry; Centre for Protein Research
- Journal of Molecular and Cellular Cardiology Plus, Vol.15(Supp.), 100727
- Elsevier
- 03/2026
- International Society for Heart Research (ISHR) World Congress, XXV (Nara, Japan, 11/05/2025–14/05/2025)
- Copyright © The Author(s) 2026. This work was first published in Journal of Molecular and Cellular Cardiology Plus (Elsevier). This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial use, distribution and reproduction in any medium, provided the original work is properly attributed to the creator(s) and the source, is not altered, transformed, or built upon in any way, and a link to the Creative Commons license is provided.
- English
- Conference proceeding; Conference Abstract