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

Abstract

Abstract-Previous studies show that exercise training and caloric restriction improve cardiac function in obesity.However, the molecular mechanisms underlying this effect on cardiac function remain unknown. Thus, we studied the effect of exercise training and/or caloric restriction on cardiac function and Ca 2ϩ handling protein expression in obese rats. To accomplish this goal, male rats fed with a high-fat and sucrose diet for 25 weeks were randomly assigned into 4 groups: high-fat and sucrose diet, high-fat and sucrose diet and exercise training, caloric restriction, and exercise training and caloric restriction. An additional lean group was studied. The study was conducted for 10 weeks. Cardiac function was evaluated by echocardiography and Ca 2ϩ handling protein expression by Western blotting. Our results showed that visceral fat mass, circulating leptin, epinephrine, and norepinephrine levels were higher in rats on the high-fat and sucrose diet compared with the lean rats. Cardiac nitrate levels, reduced/oxidized glutathione, left ventricular fractional shortening, and protein expression of phosphorylated Ser 2808 -ryanodine receptor and Thr 17 -phospholamban were lower in rats on the high-fat and sucrose diet compared with lean rats. Exercise training and/or caloric restriction prevented increases in visceral fat mass, circulating leptin, epinephrine, and norepinephrine levels and prevented reduction in cardiac nitrate levels and reduced:oxidized glutathione ratio. Exercise training and/or caloric restriction prevented reduction in left ventricular fractional shortening and in phosphorylation of the Ser 2808 -ryanodine receptor and Thr 17 -phospholamban. These findings show that exercise training and/or caloric restriction prevent cardiac dysfunction in high-fat and sucrose diet rats, which seems to be attributed to decreased circulating neurohormone levels. In addition, this nonpharmacological paradigm prevents a reduction in the Ser 2808 -ryanodine receptor and Thr 17 -phospholamban phosphorylation and redox status. (Hypertension. 2010;56:629-635.)

RETRACTED: Angiotensin receptor blockade improves the net balance of cardiac Ca2+ handling-related proteins in sympathetic hyperactivity-induced heart failure

“…Over the last decades, several studies have shown that ventricular dysfunction is related to changes in phosphorylation status of sarco/ endoplasmic proteins (LeWinter, 2005;Paulino et al, 2010), reduced sarcoplasmic reticulum Ca 2+ ATPase (SERCA2) function (Pogwizd et al, 2001), upregulation of Na + -Ca 2+ exchanger (NCX) (Pogwizd and Bers, 2002) and diastolic Ca 2+ leak via ryanodine receptors (Ai et al, 2005). We have reported that Ca 2+ handling impairment is associated with ventricular dysfunction and HF progression Medeiros et al, 2008), where both pharmacological (Bartholomeu et al, 2008) and non-pharmacological (Vanzelli et al, 2010) therapies improved cardiac function by minimizing Ca 2+ transient abnormalities.…”

Differences in hemodynamic response to metaboreflex activation between obese patients with metabolic syndrome and healthy subjects with obese phenotype

“…It has been reported that patients with metabolic syndrome can show signs of impaired left ventricular function during exercise (17). Furthermore, there is evidence that obesity can alter left ventricular systolic function, which has been attributed to calcium modulation during the cardiac cycle (44). However, in our experimental setting, subjects did not show any sign or symptoms of overt heart failure.…”

Ca2+ mishandling and cardiac dysfunction in obesity and insulin resistance: Role of oxidative stress

“…Assessment of cardiac contractile performance in vivo (by echocardiography or invasive LV catheterization), ex vivo (in isolated working hearts) and in vitro (isolated ventricular myocytes) in different animal models of obesity and IR has revealed mechanical abnormalities manifested as prolonged diastolic relaxation, depressed ejection fraction and decreased fractional shortening [15,16,47,48,50,[52][53][54]57,60,[81][82][83][84][85]. The molecular mechanisms underlying abnormal cardiac function in obesity and IR are still not completely understood, but may involve alterations of intracellular Ca 2+ handling since Ca 2+ cycling is the central coordinator of contraction and relaxation during the process of excitation-contraction coupling (ECC).…”