title: 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.
authors.affiliation: Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, Oregon; and.
authors.forename: Belinda H
authors.initials: BH
authors.lastname: McCully
authors.forename: Wohaib
authors.initials: W
authors.lastname: Hasan
authors.forename: Cole T
authors.initials: CT
authors.lastname: Streiff
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Houle
authors.forename: William R
authors.initials: WR
authors.lastname: Woodward
authors.forename: George D
authors.initials: GD
authors.lastname: Giraud
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Brooks
authors.forename: Beth A
authors.initials: BA
authors.lastname: Habecker
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004837:Epinephrine; D006321:Heart / Q000294:innervation*; D006325:Heart Atria / Q000294:innervation; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D009765:Obesity / Q000150:complications / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D010275:Parasympathetic Nervous System / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000254:growth & development / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D000109:Acetylcholine; D009638:Norepinephrine; D004837:Epinephrine
keywords: arrhythmia; autonomic imbalance; neurite outgrowth; obesity