The adipose tissue has long been thought to represent a passive source of triglycerides and fatty acids. However, extensive data have demonstrated that the adipose tissue is also a major endocrine organ that directly or indirectly affects the physiological functions of almost all cell types. Obesity is recognized as a risk factor for multiple systemic conditions, including metabolic syndrome, type 2 diabetes mellitus, sleep apnea, cardiovascular disorders, and many others. Obesity-related changes in the adipose tissue induce functional and structural changes in cardiac myocytes, promoting a wide range of cardiovascular disorders, including atrial fibrillation (AF). Due to the wealth of epidemiologic data linking AF to obesity, the mechanisms underlying AF occurrence in obese patients are an area of rich ongoing investigation. However, progress has been somewhat slowed by the complex phenotypes of both obesity and AF. The triad inflammation, oxidative stress, and mitochondrial dysfunction are critical for AF pathogenesis in the setting of obesity via multiple structural and functional proarrhythmic changes at the level of the atria. The aim of this paper is to provide a comprehensive view of the close relationship between obesity-induced oxidative stress, inflammation, and mitochondrial dysfunction and the pathogenesis of AF. The clinical implications of these mechanistic insights are also discussed.

Background/Objectives: We previously described a rat model of AF induced by long-term transesophageal atrial burst pacing. Here, we further characterize this model by exploring arrhythmia inducibility, spontaneous AF occurrence, and related autonomic and molecular changes. Methods: Twelve adult male Wistar rats were randomized into two groups: control (n = 5) and AF (n = 7). The rats in the AF group underwent 10 days of transesophageal atrial pacing. In the control rats, the same protocol was mimicked. Spontaneous AF occurrence and heart rate variability (HRV) were evaluated before, during, and after stimulation. Left atrial RNA levels of Hcn1, Hcn2, Hcn4, and Pitx2 were evaluated. Results: In AF, no animal presented spontaneous AF before stimulation. After stimulation initiation, all AF rats presented spontaneous AF (p = 0.08). In the AF rats, HRV analysis revealed a progressive increase in the standard deviation of the RR intervals after atrial stimulation initiation (p < 0.01). The left atrial RNA levels of Hcn4 were higher (p = 0.03) and Pitx2 levels were lower (p = 0.02) in the AF rats compared to the control group. Conclusions: This study validates our previous data and confirms the occurrence of spontaneous AF following long-term atrial pacing in rats. Relatively increased parasympathetic modulation and changes in the atrial expression of Hcn4, encoding for I_f, and Pitx2 likely play critical mechanistic roles in this model.