Obesity-associated alterations in cardiac connexin-43 and PKC signaling are attenuated by melatonin and omega-3 fatty acids in female rats

• Published in: Molecular and cellular biochemistry Vol. 454; no. 1-2; pp. 191 - 202
• Main Authors: Egan Benova, Tamara, Viczenczova, Csilla, Szeiffova Bacova, Barbara, Knezl, Vladimir, Dosenko, Victor, Rauchova, Hana, Zeman, Michal, Reiter, Russel J., Tribulova, Narcis
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.04.2019; Springer; Springer Nature B.V
• Subjects: Abnormalities; Adipose tissue; Antiarrhythmia agents; Arrhythmia; Attenuation; Biochemistry; Biomedical and Life Sciences; Body weight; Cardiac arrhythmia; Cardiology; Cholesterol; Connexin 43; Disease susceptibility; EDTA; Fatty acids; Gerontology; Heart; Kinases; Life Sciences; Medical Biochemistry; Melatonin; Obesity; Oncology; Polyunsaturated fatty acids; Protein kinase C; Protein kinases; Proteins; Rats; Risk factors; Rodents; Signaling; Sucrose; Sugar; Triglycerides; Unsaturated fatty acids; Ventricle; Melatonin; Adiposity; Omega-3 PUFA; Female rats; Sucrose diet; Cardiac connexin-43; Ventricular fibrillation
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-018-3463-0

We aimed to explore whether specific high-sucrose intake in older female rats affects myocardial electrical coupling protein, connexin-43 (Cx43), protein kinase C (PKC) signaling, miR-1 and miR-30a expression, and susceptibility of the heart to malignant arrhythmias. Possible benefit of the supplementation with melatonin (40 µg/ml/day) and omega-3 polyunsaturated fatty acids (Omacor, 25 g/kg of rat chow) was examined as well. Results have shown that 8 weeks lasting intake of 30% sucrose solution increased serum cholesterol, triglycerides, body weight, heart weight, and retroperitoneal adipose tissues. It was accompanied by downregulation of cardiac Cx43 and PKCε signaling along with an upregulation of myocardial PKCδ and miR-30a rendering the heart prone to ventricular arrhythmias. There was a clear benefit of melatonin or omega-3 PUFA supplementation due to their antiarrhythmic effects associated with the attenuation of myocardial Cx43, PKC, and miR-30a abnormalities as well as adiposity. The potential impact of these findings may be considerable, and suggests that high-sucrose intake impairs myocardial signaling mediated by Cx43 and PKC contributing to increased susceptibility of the older obese female rat hearts to malignant arrhythmias.