Role of CD36 in Palmitic Acid Lipotoxicity in Neuro-2a Neuroblastoma Cells

Elevated level of palmitic acid (PA), a long-chain saturated fatty acid (SFA), is lipotoxic to many different types of cells including Neuro-2a (N2a) neuroblastoma cells. CD36 is a multifunctional membrane glycoprotein that acts as a fatty acid translocase (FAT) facilitating the transport of long-chain free fatty acids (FFAs) into cells, serves a fatty acid (FA) sensing function in areas including taste buds and the proximal gut, and acts as a scavenger receptor that binds to many ligands, including FAs, collagen, oxidized low-density lipoproteins, and anionic phospholipids. However, the involvement of CD36 in FA uptake and PA lipotoxicity in N2a cells remains unclear. In this study, we examined FA uptake in BSA- and PA-treated N2a cells and investigated the involvement of CD36 in FA uptake and PA lipotoxicity in N2a cells. Our data showed that PA treatment promoted FA uptake in N2a cells, and that treatment with sulfo-N-succinimidyl oleate (SSO), a CD36 inhibitor, significantly decreased FA uptake in BSA- and PA-treated N2a cells, and ameliorated PA-induced decrease of cell viability, decrease of diploid cells, and increase of tetraploid cells. We also found that CD36 knockdown significantly decreased FA uptake in both BSA- and PA-treated cells as compared to their corresponding wild-type controls, and dramatically attenuated PA-induced cell cycle defects in N2a cells. Our data suggest that CD36 may play a critical role in FA uptake and PA lipotoxicity in N2a cells. CD36 may therefore represent a regulatory target against pathologies caused by excess FAs.

Automated summary

The study revealed that CD36 plays a crucial role in fatty acid uptake and palmitic acid (PA) lipotoxicity in N2a neuroblastoma cells, suggesting that CD36 may represent a regulatory target against pathologies caused by excess fatty acids.