Cardiac remodeling and higher sensitivity to ischemia-reperfusion injury in female rats submitted to high-fat high-sucrose diet: an in vivo / ex vivo longitudinal follow-up

International audience ; Prediabetes is an important risk factor for type 2 diabetes and cardiovascular complications, such as myocardial infarction. However, few studies explore female sexin this context. Here, we aim to investigate the effects of high-fat high-sucrose diet on cardiac parameters and sensitivity to ischemia-reperfusion injury of female Wistar rats.Female Wistar rats received for 5 months normal diet (CTRL group) or high-fat high-sucrose diet (HFS group). Every month MRI was performed to follow myocardial morphology, function and perfusion; cardiac and hepatic triglyceride content; and amount of sub-cutaneous and visceral adipose tissues.Then, ex vivoexperiments were performed on isolated perfused heartsto evaluate tolerance to ischemia-reperfusion, with simultaneous measurement of energy metabolism by 31P MRS and contractile function. Coronary flow was measured before and after ischemia.At the end of the experiments, hearts were freeze-clamped for biochemical assays. Five months of high-fat high-sucrose diet induced a prediabetic condition in female Wistar rats, associated with an increase in myocardial perfusion, systolic and diastolic wall thickness. HFS rats also exhibited higher sensitivity to ischemia-reperfusion injury in comparison to controls, characterized by impaired cardiac function, energy metabolism and endothelial function. Biochemical analyses in hearts highlighted eNOS uncoupling, higher malondialdehyde level and lower S-Glutathionylation of proteinsin HFS rats,indicating higher oxidative stress. Prediabetes induced by energy-densediet was associated with modification of cardiac morphology and higher myocardial sensitivity to ischemia-reperfusion injury. These results may be related to the high risk of cardiovascular complications among type 2diabetic women.