These results suggest that GSK-3α promotes lipid anabolism through PPARα-Ser280 phosphorylation, which underlies the development of lipotoxic cardiomyopathy in the context of obesity.
FABP3 has been proposed as a circulating clinical biomarker for cardiomyopathy and muscle toxicity, as well as a preclinical marker for PPARα-induced muscle toxicity.
The aim of the present study was to investigate the effects of fenofibrate, a peroxisome proliferator-activated receptor-α (PPARα) activator, on cell hypertrophy and adiponectin expression in vitro and in a rat model of daunorubicin-induced cardiomyopathy.
Together, these findings suggest that ARNT is a critical regulator of myocardial FA metabolism and that its deletion leads to CM and an increase in triglyceride accumulation through PPARα.
Our results indicate a critical role for PPARalpha in myocardial pump function and suggest that mouse models combining different genetic effects such as PPARalpha knockout mice overexpressing muscle LPL may be useful to study cardiomyopathies.