(A) Micrographs and spheres count in 83 Ctrl, AMPKa1, and AMPKa2 thirty days following two rounds of transduction with shCtrl or shSCD lentivirus. Scale bar, 50μm. (B) 83-Fluc Ctrl or AMPKa1 GSCs were transduced with shCtrl or shSCD1 and intracranially implanted in mice (n=3). Representative images and longitudinal Fluc imaging of mice in each group. (C) Total lipids in untreated (DMSO) and treated (YTX) 83 Ctrl/AMPK for 72h. (D) Desaturation index (DI) of 16:0 and 18:0 in 83 Ctrl/AMPK treated with YTX-7739 for 72h. (E) PCA of individual lipid species from untreated and treated 83 Ctrl/AMPK. Percentage of total variance explained by individual principal components (PC1 and PC2). (F) Fluorescence imaging and quantification of lipid droplets (LD) in GSC expressing Ctrl, AMPKa1, and AMPKa2. Scale bar, 25 μm (G) Heatmap of CE and DG after YTX-7739 treatment for 72h. (H) The amount of TG with 0–10 carbon bonds in 83 Ctrl/AMPK treated with YTX-7739 for 72h. (I) Relative expression of UPR markers in 83 supplemented with BSA or C16:0 (300μM) ± OAG (60μM). (J) Immunoblot analysis of 83 treated with YTX-7739 (1μM) ± OAG. (K) Cell viability of M76 co-treated with YTX-7739 (0.5μM) and OAG (60μM) in addition to DGAT1i and GAT2i for 96h. ****P<0.0001; *** P<0.001; **P<0.01; *P<0.05; ns, not significant.