In vivo and ex vivo longitudinal follow-up of resveratrol supplementation or restauration of a normal diet in female rat hearts submitted to high-fat-high-sucrose diet

Abstract

Prediabetic women are at greater risk of cardiovascular diseases than men, investigating new sex dependent strategic therapies is then essential to limit cardiovascular complications in prediabetic women. We aimed to evaluate the effects of resveratrol supplementation (RSV) or restauration of a standard diet on the heart of prediabetic female rats submitted to high-fat-high-sucrose diet (HFS). Wistar female rats were divided in 4 groups fed for 5 months with: normal or HFS diet (CTRL/HFS), HFS with RSV (1 mg/kg/day) during the last 2 months or HFS for 3 months and 2 months of standard diet (RSD). We performed a longitudinal in vivo study of cardiac function, morphology and perfusion by MRI, then rats underwent an IPGTT. Ex vivo experiments on isolated perfused hearts were realized to study cardiac function [rate pressure product (RPP), end diastolic pressure (EDP)] and energy metabolism with 31 P magnetic resonance spectroscopy during an ischemia-reperfusion injury (IR). Tissues were collected for analyzes. Five months of HFS diet-induced glucose intolerance ( P < 0.05), increased heart perfusion and heart/tibia length ratio (HTLR) ( P < 0.01 vs. CTRL). HFS also induced altered myocardial tolerance to IR, characterized by impaired RPP and EDP ( P < 0.001) associated with lower ATP and PCr levels during reperfusion ( P < 0.001, P < 0.05 vs. CTRL). RSV had no effect on glucose tolerance and heart perfusion ( P < 0.01 vs. CTRL) but normalized HTLR to CTRL level. Interestingly, RSV diminished EDP during reperfusion ( P < 0.05 vs. HFS). RSD normalized glucose tolerance without effect on heart perfusion and HTLR ( P < 0.01 and P < 0.05 vs. CTRL). RSD improved tolerance to IR with increased RPP ( P < 0.05 vs. HFS), ATP and PCr levels during reperfusion ( P < 0.01, P < 0.001 vs. HFS). The two approaches have distinct effects on cardiac function and energy metabolism of prediabetic female rats. Further studies are on the go to explore the mechanisms involved.