Palmitate induces myocardial lipotoxic injury via the endoplasmic reticulum stress-mediated apoptosis pathway

Increased free fatty acids in cardiomyocytes induce myocardial lipotoxic injury, but the underlying mechanisms are not well understood. Therefore, the aim of the present study was to explore the role of the endoplasmic reticulum (ER) stress‑mediated apoptosis pathway in palmitate (PA)‑induced cardiomyocyte lipotoxicity. H9c2 cells were treated with various doses (100, 200 and 400 µM) of PA to mimic cardiomyocyte lipotoxicity in vitro. Oil Red O staining was used to determine the accumulation of intracellular lipids. An MTT assay was used to determine the cell viability. Lactate dehydrogenase (LDH) activity was used to measure the injury of H9c2 cells. Flow cytometry analysis was used to detect apoptosis. Western blotting was used to evaluate the expression change of ER stress‑mediated apoptosis pathway proteins, including 78 kDa glucose‑regulated protein (GRP78), eukaryotic initiation factor 2 α (eIF2α), protein kinase R‑like endoplasmic reticulum kinase (PERK), C/EBP homologous protein (CHOP) and cleaved caspase‑12. The results demonstrated that various doses of PA promoted excessive lipid deposition in cardiomyocytes and resulted in decreased cell viability, and increased the LDH activity and apoptosis rate in a dose‑dependent manner. Furthermore, the expression of GRP78, a marker of ER stress, and the phosphorylation of eIF2α and PERK were increased following treatment with PA. Notably, the levels of CHOP and cleaved caspase‑12, critical regulators of ER stress‑mediated apoptosis pathway, were also elevated, and this effect was reversed by a specific ER stress inhibitor (4‑phenyl butyric acid). In conclusion, the results of the current study demonstrated that PA induces myocardial lipotoxic injury by triggering ER stress and the ER stress‑mediated apoptosis pathway.