Fine particles cause the abnormality of cardiac ATP levels via PPARɑ-mediated utilization of fatty acid and glucose using in vivo and in vitro models

Abstract

Ambient fine particle (PM2.5) is one of the potential risk factors for the cardiovascular disease, which is characterized by a marked shift in energy substrate preference leading to the reduction of adenosine triphosphate (ATP) synthesis. The metabolic adaptation is brought about by alterations in substrate transporters. Hence, this study aimed to investigate the effects and possible mechanisms of seasonal PM2.5 exposure on alteration of cardiac ATP content. Sprague Dawley (SD) rats were exposed to summer and winter PM2.5 for two months to generate a cardiac damage phenotype, characterized by apoptosis, lipid peroxidation, and ATP depletion. Reduced fatty acid content and elevated glucose content were observed in haze dose PM2.5-exposed SD rats and rat cardiomyocyte cells. Expressions of their transporters in PM2.5-treated groups exhibited the homologous trends. Moreover, PM2.5 exposure repressed the expression and translocation of peroxisome proliferator-activated receptor alpha (PPARα) in a dose-dependent manner. However, the addition of WY-14643 (an inhibitor of PPARα) prominently alleviated the above phenomenons. The effect of PM2.5 in winter was found to be more serious than in summer. These results demonstrated that seasonal PM2.5 exposure causes the abnormality of cardiac ATP generation through the regulation of PPARα-mediated selection and utilization of energy substrates and their transporters. This study contributes in better understanding of haze-induced cardiovascular disease by revealing crucial indicators involved in this phenomenon.