ApoTransferrin Induces Accumulation of Lipid Droplets in Oligodendroglial Cell

Transferrin is the principal iron-carrier protein and is primarily synthesized in the liver, oligodendrocytes (OLG), and choroid plexus. We previously demonstrated that apotransferrin (aTf) treatment induces OLG maturation in vitro and in vivo. Given that approximately 80% of myelin consists of lipids, predominantly cholesterol, tight regulation of lipid metabolism is essential during myelin formation. Lipid droplets (LDs) are dynamic intracellular organelles that store fatty acids as neutral lipids, including triglycerides and cholesterol esters. Recent studies have demonstrated the presence and regulated turnover of LDs in glial cells, suggesting roles in both physiological and pathological processes. During OLG maturation, the demand for lipid synthesis increases markedly to sustain membrane expansion and myelin production. Because this high lipid demand, we hypothesized that aTf-induced OLG maturation is associated with metabolic reprogramming involving lipid droplet dynamics, which may serve as a source of fatty acids for membrane biogenesis and energy production. In this context, LDs may represent a critical metabolic hub through which OLGs regulate lipid homeostasis and adapt to increased bioenergetic demands. However, the mechanisms governing LD biogenesis and turnover in oligodendroglial cells during development and under different metabolic conditions remain poorly understood. Importantly, LDs are now recognized as active participants in cellular metabolism, stress responses, and membrane biogenesis rather than passive lipid storage compartments. The aim of this study is to characterize LD dynamics, as well as specific lipid and protein profiles, in the Oli-Neu cell line and in oligodendroglial cells during the maturation process in the presence of aTf. We specifically investigate whether the aTf-induced increase in LD abundance reflects enhanced membrane biosynthetic requirements, with augmented energy production supported by β-oxidation of fatty acids released from triglycerides stored within LDs.