The Catalytic Domain of Neuropathy Target Esterase Influences Lipid Droplet Biogenesis and Lipid Metabolism in Human Neuroblastoma Cells

As an endoplasmic reticulum (ER)-anchored phospholipase, neuropathy target esterase (NTE) catalyzes the deacylation of lysophosphatidylcholine (LPC) and phosphatidylcholine (PC). The catalytic domain of NTE (NEST) exhibits comparable activity to NTE and binds to lipid droplets (LD). In the current study, the nucleotide monophosphate (cNMP)-binding domains (CBDs) were firstly demonstrated not to be essential for the ER-targeting of NTE, but to be involved in the normal ER distribution and localization to LD. NEST was associated with LD surface and influenced LD formation in human neuroblastoma cells. Overexpression of NEST enhances triacylglycerol (TG) accumulation upon oleic acid loading. Quantitative targeted lipidomic analysis shows that overexpression of NEST does not alter diacylglycerol levels but reduces free fatty acids content. NEST not only lowered levels of LPC and acyl-LPC, but not PC or alkyl-PC, but also widely altered levels of other lipid metabolites. Qualitative PCR indicates that the increase in levels of TG is due to the expression of diacylglycerol acyltransferase 1 gene by NEST overexpression. Thus, NTE may broadly regulate lipid metabolism to play roles in LD biogenesis in cells.