Abstract 5082: Exercise Training Associated With Hypocaloric Diet Restores Calcium Handling Proteins Expression and Cardiac Function in Obese Rats
Introduction. Obesity is a worldwide health problem associated with increased leptin levels, insulin resistance and sympathetic hyperactivity, which ultimately leads to cardiac dysfunction. Exercise training and hypocaloric diet are known to improve cardiac function associated with decreased leptin levels and sympathetic activity. However, the molecular mechanisms underlying improved cardiac function by exercise training, hypocaloric diet or both are unknown. We tested the hypothesis that exercise training and hypocaloric diet in obese rats would increase cardiac function by improving the net balance of cardiac Ca2+ handling proteins.
Methods. Male Wistar rats (30 days-old) were fed with standard chow (C) or cafeteria diet with high-fat for 25 weeks. Then the rats fed with cafeteria diet were randomly assigned into 4 groups: high-fat-chow for 10 weeks (O); high-fat-chow submitted to running exercise training (60% VO2max) for 10 weeks (OT); food restriction (20% less intake of standard chow) for 10 weeks (OR); and exercise training and food restriction for 10 weeks (OTR). Cardiac function was evaluated by echocardiography and protein expression by Western blotting.
Results. Body weight (470±17 vs. 414±13g, P<0.01), adiposity index (8±0.5 vs. 5±0.3%, P<0.001) and leptin levels (6±0.8 vs. 3±0.3 ng/dL, P<0.001) were higher and left ventricular fractional shortening (LVFS) lower (39±1 vs. 44±1%, P<0.05) in O compared to C. Protein expression of phosphorylated-Ser2809-ryanodine receptor (−48%, P-RyR Ser2809/RyR) and phosphorylated PLB Thr17-phospholamban (−25%, P-PLB Thr17/PLB) was lower in O compared to C. Both hypocaloric diet and exercise increased phosphorylation of RyR and PLB and, in addition, left ventricular function shortening. Hypocaloric diet decreased body weight (17%), adiposity index (50%) and leptin levels (56%) whereas exercise decreased adiposity index (25%) and improved VO2max (52%).
Conclusion. Obesity-induced cardiac dysfunction is associated with reduced phosphorylation of sarcoplasmic reticulum proteins, which are essential to cardiac Ca2+ handling. Nonpharmacological therapy based on exercise training and hypocaloric diet restores the phophorylated levels of these proteins and improves cardiac function.