Inhibition of endoplasmic reticulum stress prevents high‐fat diet mediated atrial fibrosis and fibrillation

• Published in: Journal of Cellular and Molecular Medicine Vol. 24; no. 23; pp. 13660 - 13668
• Main Authors: Zhang, Yan, Yang, Shuwen, Fu, Jing, Liu, Annan, Liu, Deping, Cao, Suyan
• Format: Journal Article
• Language: English
• Published: England Wiley 01.12.2020; John Wiley & Sons, Inc; John Wiley and Sons Inc
• Subjects: Age; Aged; Animals; Arrhythmia; Atrial Fibrillation; Atrial Fibrillation - diagnosis; Atrial Fibrillation - etiology; Atrial Fibrillation - metabolism; Atrial Fibrillation - prevention & control; atrial fibrosis; Atrium; Biomarkers; Body mass index; Body weight; Cardiac arrhythmia; Cardiovascular disease; CHOP protein; Chronic obstructive pulmonary disease; Collagen; Comorbidity; Coronary vessels; Diabetes; Diet, High-Fat; Diet, High-Fat - adverse effects; Disease Models, Animal; Disease Susceptibility; Echocardiography; Electrical stimuli; Electrocardiography; Endoplasmic reticulum; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Endoplasmic Reticulum Stress - drug effects; Female; Fibrillation; Fibrosis; Glucose; Heart Atria; Heart Atria - drug effects; Heart Atria - pathology; Heart Atria - physiopathology; High fat diet; Humans; Immunohistochemistry; Incidence; Laboratory animals; Male; Mice; Middle Aged; Morbidity; Normal distribution; Obesity; Obesity - complications; Obesity - metabolism; Original; Original Articles; Overweight; Overweight - complications; Overweight - metabolism; Phenylbutyric acid; Proteins; Risk factors; Software; Statistical analysis; Weight control; atrial fibrosis; atrial fibrillation; endoplasmic reticulum stress; high-fat diet
• ISSN: 1582-1838; 1582-4934; 1582-4934
• DOI: 10.1111/jcmm.15816

Obesity is a significant risk factor for atrial fibrillation (AF), which is the most common sustained arrhythmia with increased mortality and morbidity. High‐fat diet (HFD)‐induced obesity is associated with the activation of endoplasmic reticulum stress (ERS). However, the role of ERS in HFD‐induced AF remains elusive. Human atrium samples were examined for the ERS activation test. C57BL/6J mice were divided into four groups, including the control group, the HFD group, the 4‐phenylbutyric acid (4‐PBA) group, and the HFD + 4‐PBA group. At the age of 4 weeks, the HFD group and the HFD + 4‐PBA group were given HFD to construct the obesity model, while the other two groups were given a normal diet (ND). Transesophageal programmed electrical stimulation was conducted to evaluate the AF inducibility and duration. Atrial fibrosis and ERS activation were also investigated.We found that CHOP and GRP‐78 protein were significantly higher in overweight patients than the controls (both P < 0.05). AF inducibility and duration of the HFD group were significantly higher than the other groups (both P < 0.05), while there was no difference between those groups (P > 0.05). The mice of the HFD group had significantly higher collagen volume fraction (CVF%) than the other groups (P < 0.05). ERS marker protein of GRP78, p‐PERK, ATF6 and CHOP protein expression level was increased in the HFD group, which were significantly mitigated in the HFD + 4‐PBA group. In summary, HFD‐induced ERS activation facilitates atrial fibrosis and AF. The inhibition of ERS might alleviate atrial fibrosis and reduce the incidence of AF‐associated obesity.