High-fat diet induces cardiomyocyte apoptosis via the inhibition of autophagy

Excessive fat intake induces obesity and causes cardiac injury. Intracellular degradation process involving destruction of long-lived proteins and organelles maintains homeostasis for cells under stress. The purpose of this study was to explore the relation of high-fat diet (HFD)-induced cardiac injury and intracellular degradation process with regard to autophagy and ER stress. HFD feeding for 24 weeks induced hyperglycemia, hyperlipidemia, and cardiac hypertrophy in adult male C57BL/6 mice. In the heart, PARP cleavage, an indicator of apoptosis, levels of LC3-II and p62, indicators of autophagy, and CHOP, indicator of ER stress, were increased. A palmitate-treated cardiomyoblast (H9C2) cell culture was examined to explore how HFD induced myocardial injury. Excessive palmitate (400 mu M) treatment induced apoptosis and increased the number of autophagosomes and acid vacuoles of H9C2 cells. Besides, it elevated the expression of LC3-II, p62, and PARP cleavage. Induction of autophagy by rapamycin ameliorated palmitate-induced apoptosis, while inhibition of autophagy by 3-methyladenine or LC3 siRNA exacerbated palmitate-induced apoptosis. Palmitate treatment also induced CHOP expression which is associated with ER stress. HFD can cause cardiac injury by induction of apoptosis which is associated with autophagy dysregulation and ER stress. In addition, autophagy deficiency augments cardiac apoptosis, suggesting that autophagy serves as a pro-survival role in lipotoxic condition.