Melatonin increases susceptibility to atrial fibrillation in obesity via Akt signaling impairment in response to lipid overload. Issue 3 (23rd January 2023)

• Record Type: Journal Article
• Authors: Qin, Xinghua; Fu, Yuping; Fan, Jiali; Liu, Binghua; Liu, Peng; Zhang, Yudi; Jiang, Tiannan; Zheng, Qiangsun
• Is Part Of: Journal of pineal research. Volume 74:Issue 3(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-01-23
• Subjects: atrial fibrillation -- insulin sensitivity -- melatonin -- metabolism -- obesity -- protein kinase B -- Randle cycle; Pineal gland -- Periodicals; Pineal Gland -- Periodicals; Épiphyse (Glande); Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 612.492
• DOI: 10.1111/jpi.12851
• Languages: English
• ISSNs: 0742-3098

Abstract

Abstract: Melatonin has been proven to have antiarrhythmic potential; however, several studies have recently challenged this view. Herein, using a mouse model of obesity‐induced atrial fibrillation (AF), we tentatively explored whether exogenous melatonin supplementation could increase AF susceptibility in the context of obesity. We observed that an 8‐week drinking administration of melatonin (60 µg/ml in water) induced a greater susceptibility to AF in obese mice, although obesity‐induced structural remodeling was alleviated. An investigation of systemic insulin sensitivity showed that melatonin treatment improved insulin sensitivity in obese mice, whereas it inhibited glucose‐stimulated insulin secretion. Notably, melatonin treatment inhibited protein kinase B (Akt) signaling in the atria of obese mice and palmitate‐treated neonatal rat cardiomyocytes, thereby providing an AF substrate. Melatonin increased lipid stress in obesity, as evidenced by elevated lipid accumulation and lipolysis‐related gene expression, thus contributing to the impairment in atrial Akt signaling. Taken together, our results demonstrated that melatonin could increase AF susceptibility in obesity, probably due to increased lipid stress and resultant impairment of atrial Akt signaling. Our findings suggest that special precautions should be taken when administering melatonin to obese subjects.