Fig. 6

Overview of C8 and C10 metabolism in brain slices. (1) Both C8 and C10 metabolism was unaffected by the carnitine palmitoyltransferase I (CPT-1) inhibitor etomoxir. (2) When provided alone, the extent of C8 and C10 metabolism was comparable, but when provided together C10 was preferred over C8 as a metabolic substrate. (3) In cultured astrocytes, C8 selectively increased the respiration linked to ATP production, whereas the presence of C10 elevated the mitochondrial proton leak. (4) Both C8 and C10 is utilized for glutamine synthesis. Since glutamine is selectively synthesized in astrocytes, this signifies that astrocytes are the primary cellular compartment for C8 and C10 metabolism. (5) When glutamine synthesis from C8 and C10 metabolism was inhibited, a selective reduction was observed in neuronal GABA synthesis. This demonstrates that the glutamine generated by astrocyte metabolism of C8 and C10 is used for neuronal GABA synthesis. (6) The ketone body β-hydroxybutyrate (βHB) did not compete, to any significant extent, with C8 and C10 metabolism supporting the notion that ketone bodies are primarily utilized by neurons