Oxidative Stress, Inflammation, and Mitochondrial Dysfunction: A Link between Obesity and Atrial Fibrillation

Abstract

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.

Impact of Body Mass Index in the Cardioverter Efficacy of Amiodarone in Persistent Atrial Fibrillation

“…Additionally, sympathetic nervous system overactivity and activation of the renin-angiotensin-aldosterone system promote atrial electrical instability and fibrosis, predisposing obese individuals to AF. These interrelated mechanisms illustrate the complexity of obesity’s role in AF development and underscore the importance of therapeutic approaches aimed at mitigating these pathological processes in the prevention and management of AF in obese patients [ 31 , 32 ].…”

Investigating the Causal Link between Rheumatoid Arthritis and Atrial Fibrillation in East Asian Populations: A Mendelian Randomization Approach

“…Recent studies have highlighted the role of chronic inflammation in promoting atrial structural remodeling. Inflammatory cytokines such as TNF and IL-6 can induce fibroblast proliferation and extracellular matrix deposition, leading to atrial fibrosis [ 33 ]. This fibrotic remodeling disrupts the normal atrial architecture, creating a substrate for reentrant circuits and increasing the likelihood of AF [ 34 ].…”

Obesity Is Associated with Oxidative Stress Markers and Antioxidant Enzyme Activity in Mexican Children

“…Reactive oxygen species, the primary oxidant component in the human body, are produced in the normal metabolic process. However, in excessive adiposity, it has been documented that reactive oxygen species levels increase and exceed the capacity of the antioxidant system [7,8], where the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) play an important role [9]. Preclinical, clinical, and epidemiological studies have reported the association between metabolic diseases and oxidative stress through an accumulation of products of lipid and protein oxidation and reduced activity of the antioxidant systems [6,10].…”