Triphenyl phosphate modulated saturation of phospholipids: Induction of endoplasmic reticulum stress and inflammation

Although triphenyl phosphate (TPHP) has been reported to disrupt lipid metabolism, the effect of TPHP on lipid saturation remains unexplored. In this study, a lipidomic analysis demonstrated decreases in the levels of poly-unsaturated phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS) in RAW264.7 murine macrophage cells exposed to 10 mM TPHP. The expression of the gene encoding lysophosphatidylcholine acyltransferase 3 (Lpcat3) was significantly downregulated by 0.76 +/- 0.03 and 0.70 +/- 0.08-fold in 10 and 20 mu M TPHP exposure groups, relative to the control group. This finding explains the observed decrease in lipid saturation. Correspondingly, exposure to 10 and 20 mu M TPHP induced endoplasmic reticulum (ER) stress and inflammatory responses, which have been linked to metabolic dysfunction such as insulin resistance and hypertriglyceridemia. Therefore, TPHP may pose a risk to human health by promoting metabolic diseases. (c) 2020 Elsevier Ltd. All rights reserved.