Combined therapy with PPAR alpha agonist and carnitine supplementation rescues the detrimental cardiomyopathy with energy metabolism disorder

Abstract

The juvenile visceral steatosis (JVS) mouse, a murine model of systemic carnitine deficiency (SCD), causes disorder of fatty acid oxidation and develops cardiac hypertrophy with lipid accumulation. We investigated the effect of fenofibrate, a PPARalpha agonist, in addition to carnitine supplementation on the hypertrophied heart in JVS mice. JVS mice were fed a normal chow, 0.1% carnitine/kg containing chow (CA), or 0.1%carnitine/kg and 0.2% fenofibrate/kg containing chow (CA + FE) from 4 weeks of age. At 8 weeks, the ventricular hypertrophy in JVS mice was more attenuated by CA + FE than by CA alone. CA + FE normalized the content of myocardial ATP and triglycerides to control levels, and prevented the deterioration of left ventricular function. Combined therapy with PPARalpha agonist and carnitine supplementation may be beneficial in treating the cardiomyopathy due to SCD. [Display omitted]