Table of Contents Author Guidelines Submit a Manuscript
Oxidative Medicine and Cellular Longevity
Volume 2018, Article ID 9389784, 19 pages
Research Article

Cardiac Autonomic Neuropathy as a Result of Mild Hypercaloric Challenge in Absence of Signs of Diabetes: Modulation by Antidiabetic Drugs

1Department of Pharmacology and Toxicology, Faculty of Medicine, The American University of Beirut, Beirut, Lebanon
2Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt

Correspondence should be addressed to Fouad A. Zouein; bl.ude.bua@51zf and Ahmed F. El-Yazbi; bl.ude.bua@88ea

Received 2 October 2017; Revised 21 November 2017; Accepted 29 November 2017; Published 31 January 2018

Academic Editor: Mohamed A. Abdelmegeed

Copyright © 2018 Ola Al-Assi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Cardiac autonomic neuropathy (CAN) is an early cardiovascular complication of diabetes occurring before metabolic derangement is evident. The cause of CAN remains elusive and cannot be directly linked to hyperglycemia. Recent clinical data report cardioprotective effects of some antidiabetic drugs independent of their hypoglycemic action. Here, we used a rat model receiving limited daily increase in calories from fat (HC diet) to assess whether mild metabolic challenge led to CAN in absence of interfering effects of hyperglycemia, glucose intolerance, or obesity. Rats receiving HC diet for 12 weeks showed reduction in baroreceptor sensitivity and heart rate variability despite lack of change in baseline hemodynamic and cardiovascular structural parameters. Impairment of cardiac autonomic control was accompanied with perivascular adipose inflammation observed as an increased inflammatory cytokine expression, together with increased cardiac oxidative stress, and signaling derangement characteristic of diabetic cardiomyopathy. Two-week treatment with metformin or pioglitazone rectified the autonomic derangement and corrected the molecular changes. Switching rats to normal chow but not to isocaloric amounts of HC for two weeks reversed CAN. As such, we conclude that adipose inflammation due to increased fat intake might underlie development of CAN and, hence, the beneficial effects of metformin and pioglitazone.