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 μM 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 μM TPHP exposure groups, relative to the control group. This finding explains the observed decrease in lipid saturation. Correspondingly, exposure to 10 and 20 μM 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.