Updated project metadata. The accumulation of lipid is a histological and biochemical hallmark of obesity-associated hepato-steatosis.Moreover, growing evidenceindicatesthathigher free fatty acids (FFAs) level in hepatocytes affects a myriad of biological processes leading to excessive metabolic imbalance, increased reactive oxygen species (ROS), deregulated autophagy, and impairment of mitochondrial and ER stress, that collectively drives cell death. Lipotoxicity and cell death mechanisms have been studied for many years. However, the molecular signals that link these two events during lipid stress remain poorly understood. From the very beginning, to systematically study hepato-lipotoxicity, HepG2 treated with PA providentially recapitulates the global lipotoxic responses, including insulin resistance to hepatocyte death. Therefore, using this cell-based model system, we pursued a comprehensive, differential quantitative approach where measurements of protein dynamics are analysed by mass spectrometry. Given that indispensable information, successive temporal phosphoproteomics dynamics are allowed us to in-depth analysis of lipotoxicity associated mechanistic network of cell death more precisely.