Sympathetic cardiac hyperinnervation and atrial autonomic imbalance in diet-induced obesity promote cardiac arrhythmias

Abstract

Obesity increases the risk of arrhythmias and sudden cardiac death, but the mechanisms are unknown. This study tested the hypothesis that obesity-induced cardiac sympathetic outgrowth and hyperinnervation promotes the development of arrhythmic events. Male Sprague-Dawley rats (250-275 g), fed a high-fat diet (33% kcal/fat), diverged into obesity-resistant (OR) and obesity-prone (OP) groups and were compared with rats fed normal chow (13% kcal/fat; CON). In vitro experiments showed that both OR and OP rats exhibited hyperinnervation of the heart and high sympathetic outgrowth compared with CON rats, even though OR rats are not obese. Despite the hyperinnervation and outgrowth, we showed that, in vivo, OR rats were less susceptible to arrhythmic events after an intravenous epinephrine challenge compared with OP rats. On examining total and stimulus-evoked neurotransmitter levels in an ex vivo system, we demonstrate that atrial acetylcholine content and release were attenuated in OP compared with OR and CON groups. OP rats also expressed elevated atrial norepinephrine content, while norepinephrine release was suppressed. These findings suggest that the consumption of a high-fat diet, even in the absence of overt obesity, stimulates sympathetic outgrowth and hyperinnervation of the heart. However, normalized cardiac parasympathetic nervous system control may protect the heart from arrhythmic events.

Should the sympathetic nervous system be a target to improve cardiometabolic risk in obesity?

“…These findings of decreased basal parasympathetic tone are consistent with observations of normal cardiac norepinephrine spillover in patients with obesity-related hypertension, despite impaired baroreflex control and increases in sympathetic activity to the kidneys and skeletal muscular vasculature (171). Recently, it was found that the consumption of a high-fat diet in rats, even in the absence of overt obesity, stimulates sympathetic outgrowth and hyperinnervation of the heart (110), and this, together with atrial autonomic imbalance, may promote the development of arrhythmic events.…”

Body Mass Index and Sudden Cardiac Death in Japanese Patients After Acute Myocardial Infarction: Data From the JCAD Study and HIJAMI‐II Registry

“…Some reports have shown QT prolongation or an increased late potential in obese patients 23, 24, 25. An autonomic disturbance was reported in obese patients,26 which may provoke arrhythmia.…”

Pathogenic Mechanisms of Atrial Fibrillation in Obesity

“…направлении имеет лишь эпидемиологический харак-тер [2,3]. Детализация механизмов развития ФП у туч-ных людей представляет важную задачу для совре-менной кардиологии, так как эти знания могут спо-собствовать разработке универсальных подходов к лечению данных пациентов.…”

“…Молекулярные механизмы симпатической гипериннервации миокарда при ожи-рении не установлены. Имеются данные о том, что при-чинами этого могут быть повышение чувствительности TrkA-рецепторов к фактору роста нервов и прямое влияние СЖК плазмы на рост нервов и развитие сим-патической гипериннервации [3].…”