Food‐restriction in obese dyslipidaemic diabetic mice partially restores basal contractility but not contractile reserve

Abstract

AimsWeight reduction programmes in morbidly obese, diabetic, and hyperlipidaemic subjects usually improve cardiac load and subsequently reverse hypertrophy. However, their effect on contractile dysfunction and impaired cardiac functional reserve is unknown. Methods and resultsThe effect of food-restriction-induced weight loss on in vivo cardiac contractility before and during beta-adrenergic stimulation was assessed using left ventricular pressure-volume analysis in a mouse model featuring obesity and Type II diabetes (ob/ob), obesity, Type II diabetes, atherogenic dyslipidaemia, and hypertension (LDLR2/2;ob/ ob), or wild-type. In addition, sarcoendoplasmic reticulum (SR) Ca 2þ reuptake, interstitial collagen accumulation, and aortic atherosclerosis were measured. Food-restriction resulted in a 54% lower weight. Weight loss largely normalized pre-and afterload in both ob/ob and LDLR2/2;ob/ob mice. Contractility and relaxation improved after weight loss, partly explained by improved SR Ca 2þ reuptake. Ventricular -vascular stiffening, interstitial collagen accumulation, and aortic atherosclerosis were less in food-restricted than in free-fed LDLR2/2;ob/ob mice. In contrast, cardiac reserve was similarly impaired in free-fed and food-restricted ob/ob and LDLR2/2;ob/ob mice. ConclusionFood-restriction in obese diabetic mice leads to improved cardiac performance by diminishing cardiac load and by ameliorating the intrinsic contractile properties of the cardiac muscle. However, cardiac reserve under dobutamine stimulation did not increase.--

ACE-inhibition, but not weight reduction restores cardiomyocyte response to β-adrenergic stimulation in the metabolic syndrome

“…Furthermore, these cellular defects are in parallel with previous in vivo studies in our laboratory and with clinical studies [1,2,6-8]. …”

“…All together, our data provide evidence for contribution of intrinsic cellular mechanisms, in recovering diastolic function after diet and ACE-I, associated with extrinsic mechanisms (eg. reduced ventricular-vascular stiffening, reduced subendothelial lipid deposition and increased endothelium-dependent relaxation) [6-11,19]. …”

“…Diet has proven to reduce cardiac hypertrophy, to ameliorate diastolic function, insulin resistance and blood pressure in MS [6-8]. ACE-I improves endothelial function, reverses cardiovascular remodeling effects and has an anti-atherosclerotic effect [9-11].…”

MiR-21 protected against diabetic cardiomyopathy induced diastolic dysfunction by targeting gelsolin

“…It is widely accepted that the systolic dysfunction which might occurred in the middle or late stage of diabetic cardiomyopathy is associated with apoptosis and fibrosis. On the other hand, many studies have reported that compared with wild type mice, db/db mice may exhibit no significant fibrosis at 12, 24, and 36 weeks old [58, 59]. In this study, systolic dysfunction and cardiac fibrosis of db/db mice were not observed, which matched with the early phase of diabetic cardiomyopathy, represented by diastolic dysfunction only.…”

Exercise Training and Caloric Restriction Prevent Reduction in Cardiac Ca 2+ -Handling Protein Profile in Obese Rats

“…However, many of the obesity studies have been conducted in genetic animal models, 11,12 which may not reflect most of human obesity causes. Thus, in the present study, we tested whether 10 weeks of exercise training and/or caloric restriction would improve cardiac function in obese rats fed with a high-fat and sucrose diet that mimics food habits of humans living in Western countries.…”