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

  • Tamara Egan Benova
  • Csilla Viczenczova
  • Barbara Szeiffova Bacova
  • Vladimir Knezl
  • Victor Dosenko
  • Hana Rauchova
  • Michal Zeman
  • Russel J. Reiter
  • Narcis TribulovaEmail author


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.


Female rats Sucrose diet Adiposity Cardiac connexin-43 Ventricular fibrillation Melatonin Omega-3 PUFA 



This work was supported by APVV-15-0119, Slovak Cardiological Society Grant and VEGA 2/0167/15, 2/0076/16 grants, and by EU Structural Fund ITMS 26230120006. Omacor was kindly provided by Dr. Branislav Obsitnik from Abbott laboratories, Slovakia. English editing was performed by Drs. Vladislava Zoldi and RJ. Reitter.

Compliance with ethical standards

Conflict of interest

There is no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Tamara Egan Benova
    • 1
  • Csilla Viczenczova
    • 1
  • Barbara Szeiffova Bacova
    • 1
  • Vladimir Knezl
    • 2
  • Victor Dosenko
    • 3
  • Hana Rauchova
    • 4
  • Michal Zeman
    • 5
  • Russel J. Reiter
    • 6
  • Narcis Tribulova
    • 1
    Email author
  1. 1.Center of Experimental Medicine, Institute for Heart ResearchSlovak Academy of SciencesBartislavaSlovakia
  2. 2.Center of Experimental Medicine, Institute of Experimental Pharmacology and ToxicologySlovak Academy of SciencesBratislavaSlovakia
  3. 3.State Key Laboratory of Molecular and Cellular BiologyBogomoletz Institute of PhysiologyKyivUkraine
  4. 4.Institute of Physiology of the Czech Academy of SciencesPragueCzech Republic
  5. 5.Department of Animal Physiology and Ethology, Faculty of Natural SciencesComenius UniversityBratislavaSlovakia
  6. 6.Department of Cellular and Structural BiologyUT Health Science CenterSan AntonioUSA

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