Impact of dietary-induced obesity on adrenergic-induced cardiomyocyte damage in rats

  • Leanda Vengethasamy Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg
  • Olebogeng H.I. Majane Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg
  • Eugene F. du Toit Department of Biomedical Sciences, Faculty of Health Sciences, University of Stellenbosch, Tygerberg
  • Gavin R. Norton Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg
  • Angela J. Woodiwiss Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg

Abstract

Although obesity is an independent risk factor for heart failure and even mild-to-moderate forms of obesity are associated with myocardial systolic dysfunction the mechanisms of the myocardial dysfunction have not been identifi ed. We assessed whether dietary-induced obesity is associated with an increased sensitivity of the myocardium to ß-adrenergic-induced cardiomyocyte apoptosis or fibrosis. To induce obesity, rats were fed a diet that promotes an increased caloric intake. Adrenergic-induced cardiomyocyte apoptosis was determined by injecting rats for 5 days with isoproterenol (0.01 mg/kg/day for 3 days and 0.02 mg/kg/day for 2 days) and then studying the degree of cardiomyocyte damage using a TUNEL assay and assessing the pathological score. Five months of feeding rats a diet that promoted the development of an increased body weight (Control=481±4.3 g, Diet=550±7.8 g, p‹0.001) and visceral fat content (Control=19.6±0.8 g, Diet=33.0±1.2 g, p‹0.0001), did not alter baseline cardiomyocyte apoptosis. However, 5 days of ß-adrenergic activation resulted in an enhanced cardiomyocyte apoptosis in rats receiving the experimental diet as compared to rats receiving a normal diet (p‹0.01). No changes in the myocardial pathological score (fibrosis) were noted. The enhanced adrenergic-induced cardiomyocyte apoptosis in obese rats could not be explained by dietary-induced increases in baseline left ventricular internal diameters, decreases in systolic function (endocardial or midwall fractional shortening) or differences in the response of the heart to adrenergic-induced increases in inotropic or chronotropic function. In conclusion, the present study suggests that obesity may contribute to myocardial dysfunction by increasing the sensitivity of the myocardium to adrenergic-induced cardiomyocyte damage.
Published
2017-04-13
Section
Articles