Fig. 2: Regulation of lipid metabolism.
From: Lipid metabolism: the potential therapeutic targets in glioblastoma
Lipid metabolism is regulated by some key regulatory proteins. The regulatory mechanisms of PPARα, PPARγ, and LXRs are similar, as these receptors recruit coactivator proteins and form heterodimers with RXRs to activate lipid metabolism-associated proteins and maintain lipid homeostasis in the cells. SCAP acts as a sterol sensor, when sterol concentrations are high, sterols bind to SCAP, triggering SCAP and INSIG bind to each other, resulting in SREBPs, SCAP, and INSIG anchored in the ER. Conversely, when the sterol concentrations are low, the binding of SCAP and INSIG getting lost, and SCAP escorts SREBPs from the ER to the Golgi apparatus. There, the proteases S1P and S2P cleave SREBPs, releasing its N-terminal domain, which enters the nucleus and transcriptionally activates genes related to lipophagy and lipogenesis. The regulation of lipid metabolism is a complex and multifaceted process. Dysregulation of lipid metabolism regulatory mechanisms can contribute to glioblastoma tumorigenesis.
