Resveratrol mediated cardioprotection in obese rats
Lieben Louis, Xavier
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Obesity is a major epidemic and an independent risk factor for heart disease. Food derived compounds such as resveratrol has been reported to have strong medicinal properties and shown potential in preventing and reversing heart diseases. This study investigated the cardioprotective properties of resveratrol in an animal model of diet induced obesity and possible cellular mechanisms. Obese prone (OP) and obese resistant (OR) rats were fed with high fat diet while, sprague dawley (SD) rats that served as control were fed with normal lab chow for a total of 17 weeks. During the last 5 weeks of study, treatment group received resveratrol daily by oral gavage at a dosage of 2.5 mg/kg body weight. Treatment with resveratrol significantly improved cardiac isovolumic relaxation time (IVRT), thiobarbituric acid reactive substance (TBARS), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), triglycerides, glucose, low density lipoprotein and increased insulin in OP rats and TNF-α, glucose and leptin in OR rats. Cardiac calcium handling proteins such as sarcoendoplasmic reticulum Ca2+-ATPase2a (SERCA2a), phospholamban (PLB) and phosphorylated PLBthr17 and PLBser16 were unchanged in all the groups. Excess circulating lipids cause cellular dysfunction in major organs. Adult rat cardiomyocytes were incubated for 24 hours with different doses (10, 100 and 200µM) of palmitic acid (PA). One group cardiomyocytes were pretreated with resveratrol for 45minutes prior to addition of PA. Incubation with 200µM PA significantly increased the number of round shaped cardiomyocytes and apoptosis and resveratrol treatment prevented these changes. Cardiomyocytes contractility measurement showed 200µM PA resulted in reduced rate of relaxation and resveratrol prevented this reduction. Western blot analysis showed that the PA induced a 17% decrease in SERCA2a expression and SERCA2A:PLB ratio was preserved with resveratrol treatment. The change in SERCA2a with PA and resveratrol exposure was statistically not significant. In conclusion, resveratrol treatment reversed cardiac abnormalities in OP rats, but not in OR rats. Resveratrol treatment prevented PA induced contractile abnormality in adult cardiomyocytes. Importantly, this study showed that resveratrol can act directly on cardiomyocytes and protect against damage from exposure to high levels of lipids.