The Effects of a PPARα Agonist on Myocardial Damage in Obese Diabetic Mice With Heart Failure

Recent studies have confirmed that PPAR alpha agonists have not brought the anticipated benefits to patients with type 2 diabetes and potentially fatal heart disease We hypothesized that such agonists may have a cardio-suppressive effect in treating such disorders, therefore, we inoculated diabetic KKAy mice with encephalomyocarditis virus (EMCv) to induce a diabetic model with severe myocardial damage WY14643, a potent PPAR alpha agonist, was administered intrapentoneally either simultaneously (WY14643-late group) or 3 clays before viral inoculation (WY14643-early group) WY14643-treated mice, especially those in the WY14643-early group, had higher mortality than those in the vehicle-treated group (vehicle) in the first 5 clays after EMCv inoculation However, the survival rate in the vehicle group decreased rapidly after clay 4 and was the lowest of all 3 groups by day 9 The WY14643-treated mice showed reduced body weight and blood glucose. improved myocaichal pathological changes. lower cardiac TNF-alpha expression, and significantly higher adiponectin expression. whereas the LW/LC ratio was lower and cardiac UCP3 mRNA expression higher in the WY 14643 treatment groups than in the vehicle group on day 4 WY 14643 therefore has cardioprotective and cardio-suppressive effects when used to treat EMCv-induced myocarditis in diabetic mice The cardioprotective effect may be due to its anti-inflammatory properties and its ability to increase cardiac adiponectin expression, whereas the reduced cardiac efficiency may be clue to its enhancement of cardiac UCP3 mRNA expression (Int Heart J 2010, 51: 199-206)