[2,4-13C]β-hydroxybutyrate Metabolism in Astrocytes and C6 Glioblastoma Cells

• Published in: Neurochemical research 2011-08, Vol.36 (8), p.1566-1573
• Main Authors: Eloqayli, Haytham, Melø, Torun M., Haukvik, Anne, Sonnewald, Ursula
• Format: Article
• Language: English
• Subjects: 3-Hydroxybutyric Acid - chemistry; 3-Hydroxybutyric Acid - metabolism; Animals; Aspartic Acid - metabolism; Astrocytes; Astrocytes - cytology; Astrocytes - metabolism; Biochemistry; Biomedical and Life Sciences; Biomedicine; Brain Neoplasms - diet therapy; Brain Neoplasms - metabolism; Cell Biology; Cerebellum; Citric Acid Cycle - physiology; Diet, Ketogenic; Glioblastoma; Glioblastoma - diet therapy; Glioblastoma - metabolism; glioblastoma cells; Glucose; Glucose - metabolism; Glutamic acid; Glutamic Acid - metabolism; Glutamine; Glutamine - metabolism; High-performance liquid chromatography; Humans; Ketogenesis; Ketone bodies; Ketone Bodies - metabolism; Lactic Acid - metabolism; Magnetic resonance spectroscopy; Mass spectroscopy; Metabolism; Mice; Mitochondria; Neurochemistry; Neurology; Neurons; Neurosciences; Original Paper; Tumor Cells, Cultured
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-011-0485-3

This study was undertaken to determine if the ketogenic diet could be useful for glioblastoma patients. The hypothesis tested was whether glioblastoma cells can metabolize ketone bodies. Cerebellar astrocytes and C6 glioblastoma cells were incubated in glutamine and serum free medium containing [2,4- 13 C]β-hydroxybutyrate (BHB) with and without glucose. Furthermore, C6 cells were incubated with [1- 13 C]glucose in the presence and absence of BHB. Cell extracts were analyzed by mass spectrometry and media by 1 H magnetic resonance spectroscopy and HPLC. Using [2,4- 13 C]BHB and [1- 13 C]glucose it could be shown that C6 cells, in analogy to astrocytes, had efficient mitochondrial activity, evidenced by 13 C labeling of glutamate, glutamine and aspartate. However, in the presence of glucose, astrocytes were able to produce and release glutamine, whereas this was not accomplished by the C6 cells, suggesting lack of anaplerosis in the latter. We hypothesize that glioblastoma cells kill neurons by not supplying the necessary glutamine, and by releasing glutamate.