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

Mol Cell Biochem. 2019 Apr;454(1-2):191-202. doi: 10.1007/s11010-018-3463-0. Epub 2018 Nov 16.

Abstract

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.

Keywords: Adiposity; Cardiac connexin-43; Female rats; Melatonin; Omega-3 PUFA; Sucrose diet; Ventricular fibrillation.

MeSH terms

  • Animals
  • Anti-Arrhythmia Agents / metabolism
  • Anti-Arrhythmia Agents / pharmacology
  • Arrhythmias, Cardiac / etiology
  • Connexin 43 / metabolism*
  • Dietary Sucrose / adverse effects*
  • Fatty Acids, Omega-3 / metabolism
  • Fatty Acids, Omega-3 / pharmacology*
  • Female
  • Heart / drug effects*
  • Melatonin / metabolism
  • Melatonin / pharmacology*
  • MicroRNAs / metabolism
  • Myocardium / metabolism
  • Obesity / chemically induced
  • Obesity / complications
  • Obesity / drug therapy*
  • Obesity / metabolism
  • Protein Kinase C-delta / metabolism
  • Protein Kinase C-epsilon / metabolism
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects*

Substances

  • Anti-Arrhythmia Agents
  • Connexin 43
  • Dietary Sucrose
  • Fatty Acids, Omega-3
  • MIRN30 microRNA, rat
  • MicroRNAs
  • Protein Kinase C-delta
  • Protein Kinase C-epsilon
  • Melatonin