Influences of Unmodified and Carboxylated Carbon Nanotubes on Lipid Profiles in THP-1 Macrophages: A Lipidomics Study

Since the possible roles of surface modifications in determining multi-walled carbon nanotube (MWCNT)-promoted endoplasmic reticulum (ER) stress-mediated lipid-laden macrophage foam cell formation are still in debate, we compared unmodified and carboxylated MWCNT-induced cytotoxicity, lipid profile changes, and expression of ER stress genes in THP-1 macrophages. Particularly, we focused on lipid profile changes by using lipidomics approaches. We found that unmodified and carboxylated MWCNTs significantly decreased cellular viability and appeared to damage the cellular membrane to a similar extent. Likewise, the results from Oil Red O staining showed that both types of MWCNTs slightly but significantly induced lipid accumulation. In keeping with Oil Red O staining results, lipidomics data showed that both types of MWCNTs up-regulated most of the lipid classes. Interestingly, almost all lipid classes were relatively higher in carboxylated MWCNT-exposed THP-1 macrophages compared with unmodified MWCNT-exposed cells, indicating that carboxylated MWCNTs more effectively changed lipid profiles. But in contrast to our expectation, none of the MWCNTs significantly induced the expression of ER stress genes. Even, compared with carboxylated MWCNTs, unmodified MWCNTs induced higher expression of lipid genes, including macrophage scavenger receptor 1 and fatty acid synthase. Combined, our results suggested that even though carboxylation did not significantly affect MWCNT-induced lipid accumulation, carboxylated MWCNTs were more potent to alter lipid profiles in THP-1 macrophages, indicating the need to use omics techniques to understand the exact nanotoxicological effects of MWCNTs. However, the differential effects of unmodified and carboxylated MWCNTs on lipid profiles might not be related with the induction of ER stress.