Increased Arrhythmic Risk in Obesity Is Transduced by Adipose Tissue-Derived Extracellular Vesicles.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Obesity drives atrial fibrillation and ventricular arrhythmias, yet whether direct fat-heart communication mediates this risk is unknown. The authors demonstrate that human atrial myocytes from obese individuals exhibit prolonged action potential duration, a pro-arrhythmic phenotype reproduced by treating induced pluripotent stem cell-derived cardiomyocytes with visceral adipose tissue-derived extracellular vesicles (VAT EVs) from obese donors. VAT EVs also impaired calcium handling, activated cardiac fibroblasts, and shifted macrophages toward a pro-inflammatory activation state-collectively promoting an arrhythmogenic substrate. Using a transgenic adipose-specific EV-tracking mouse model, the authors confirmed preferential adipose-to-myocardial EV trafficking in obese vs lean mice in vivo. Transcriptome-wide association studies anchored on VAT EV-induced gene expression changes identified causal links to QT interval and atrial fibrillation in large genome-wide association studies. Pharmacologic inhibition of TRPC3, an ion channel upregulated by VAT EVs, restored action potential duration toward normal, identifying a novel therapeutic target in obesity-associated arrhythmia.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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