Metformin regulates adiponectin signalling in epicardial adipose tissue and reduces atrial fibrillation vulnerability
Open accessAbstract
Abstract Epicardial adipose tissue (EAT) remodelling is closely related to the pathogenesis of atrial fibrillation (AF). We investigated whether metformin (MET) prevents AF‐dependent EAT remodelling and AF vulnerability in dogs. A canine AF model was developed by 6‐week rapid atrial pacing (RAP), and electrophysiological parameters were measured. Effective refractory periods (ERP) were decreased in the left and right atrial appendages as well as in the left atrium (LA) and right atrium (RA). MET attenuated the RAP‐induced increase in ERP dispersion, cumulative window of vulnerability, AF inducibility and AF duration. RAP increased reactive oxygen species (ROS) production and nuclear factor kappa‐B (NF‐κB) phosphorylation; up‐regulated interleukin‐6 (IL‐6), tumour necrosis factor‐α (TNF‐α) and transforming growth factor‐β1 (TGF‐β1) levels in LA and EAT; decreased peroxisome proliferator‐activated receptor gamma (PPARγ) and adiponectin (APN) expression in EAT and was accompanied by atrial fibrosis and adipose infiltration. MET reversed these alterations. In vitro , lipopolysaccharide (LPS) exposure increased IL‐6, TNF‐α and TGF‐β1 expression and decreased PPARγ/APN expression in 3T3‐L1 adipocytes, which were all reversed after MET administration. Indirect coculture of HL‐1 cells with LPS‐stimulated 3T3‐L1 conditioned medium (CM) significantly increased IL‐6, TNF‐α and TGF‐β1 expression and decreased SERCA2a and p‐PLN expression, while LPS + MET CM and APN treatment alleviated the inflammatory response and sarcoplasmic reticulum Ca 2+ handling dysfunction. MET attenuated the RAP‐induced increase in AF vulnerability, remodelling of atria and EAT adipokines production profiles. APN may play a key role in the prevention of AF‐dependent EAT remodelling and AF vulnerability by MET.
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In a canine model of atrial fibrillation induced by rapid pacing, metformin reverses the alteration in the adipokine profile of EAT.
“In a canine model of atrial fibrillation induced by rapid pacing, metformin was able to reverse the alteration in the adipokine profile of EAT [158].”
From Dysregulated epicardial adipose tissue as a risk factor and potential therapeutic target of heart failure with preserved ejection fraction in diabetes (2022) · cites this paper as [158]
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- Authors
- Li, B., Po, S. S., Zhang, B., Bai, F., Li, J., Qin, F., Liu, N., Sun, C., Xiao, Y., Tu, T., Zhou, S., & Liu, Q.
- Affiliations
- Central South University (CN)
- University of Oklahoma Health Sciences Center (US)
- Corresponding author
- Liu, Qiming
- Venue
- Journal of Cellular and Molecular Medicine
- Publisher
- Wiley
- Published
- 2020-05-22
- Volume
- 24
- Issue
- 14
- Pages
- 7751-7766
- ISSN
- 1582-1838 (ISSN-L)
- 1582-4934
- PMC
- PMC7348162
- OpenAlex
- W3026964594
- Cited by
- 63
- References
- 60
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 13 · 2023: 9 · 2022: 9 · 2021: 9 · 2020: 2
- FWCI
- 4.49
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Cellular and Molecular Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81570310,, 81770337, 81600273)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- metformin, adiponectin, epicardial adipose tissue, atrial fibrillation, atrial remodeling, atrial fibrosis, atrial pacing, effective refractory period, inflammatory cytokines, PPARγ, reactive oxygen species, NF-κB, SERCA2a, phospholamban, lipopolysaccharide, canine model
- MeSH terms
- Adipose Tissue, Animals, Atrial Fibrillation, Calcium, Disease Models, Animal, Disease Susceptibility, Dogs, Electrocardiography, Metformin, Pericardium, Signal Transduction, Biomarkers, Cytokines, Reactive Oxygen Species, Adipocytes, Inflammation Mediators, Myocytes, Cardiac, 3T3-L1 Cells, Mice, Adiponectin, Atrial Remodeling
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