Exercise with calorie restriction improves cardiac function via attenuating mitochondrial dysfunction in ovariectomized prediabetic rats

摘要

Obesity and menopause are known as a major risk factor in the development of left ventricular (LV) dysfunction. Calorie restriction (CR) or exercise (Ex) improved metabolic status and LV function. This study aims to investigate the combined effects of Ex and CR on the cardiometabolic status, and cardiac calcium ([Ca2+]i) regulation in estrogen-deprivation, obese prediabetic rats. Female rats were fed with either a high-fat diet (HFD) or a normal diet for 13 weeks. The HFD rats were ovariectomized (HFO), and subjected to 1) vehicle (HFOV); 2) calorie restriction (HFOCR); 3) exercise (HFOEx); 4) combined therapy (HFOCB); or 5) estrogen (HFOE2). After six weeks of interventions the cardiometabolic status, cardiac [Ca2+]i transients, mitochondrial function and dynamics were determined. HFD-fed rats developed insulin resistance as indicated by increased plasma insulin and HOMA index. Although rats in the HFOV groups had markedly reduced %LVFS which indicated impaired LV function, impaired [Ca2+]i homeostasis, cardiac mitochondrial function and their dynamics, all interventions attenuated these impairments. Interestingly, HFOCB rats were observed to have the greatest cardiometabolic improvement. The combination of calorie restriction and exercise exerted greater efficacy in attenuating LV dysfunction through an improved metabolic status, cardiac function, mitochondrial function, and cardiac [Ca2+]i homeostasis than Ex or CR monotherapy in ovariectomized obese prediabetic rats.