PT  - JOURNAL ARTICLE
AU  - Jantzen Sperry
AU  - Michael C. Condro
AU  - Lea Guo
AU  - Daniel Braas
AU  - Nathan Vanderveer-Harris
AU  - Kristen K.O. Kim
AU  - Whitney B. Pope
AU  - Ajit S. Divakaruni
AU  - Albert Lai
AU  - Heather Christofk
AU  - Maria G. Castro
AU  - Pedro R. Lowenstein
AU  - Janel E. Le Belle
AU  - Harley I. Kornblum
TI  - Glioblastoma utilizes fatty acids and ketone bodies for growth allowing progression during ketogenic diet therapy
AID  - 10.1101/659474
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 659474
4099  - http://biorxiv.org/content/early/2020/08/11/659474.short
4100  - http://biorxiv.org/content/early/2020/08/11/659474.full
AB  - Glioblastoma (GBM) metabolism has traditionally been characterized by a primary dependence on aerobic glycolysis, prompting the use of the ketogenic diet (KD) as a potential therapy. In this study we evaluated the effectiveness of the KD in GBM and assessed the role of fatty acid oxidation (FAO) in promoting GBM propagation. In vitro assays revealed FA utilization throughout the GBM metabolome, and growth inhibition in nearly every cell line in a broad spectrum of patient-derived glioma cells treated with FAO inhibitors. In vivo assessments revealed that knockdown of carnitine palmitoyltransferase 1A (CPT1A), the rate limiting enzyme for FAO, reduced the rate of tumor growth and increased survival. However, the unrestricted ketogenic diet did not reduce tumor growth, and for some models significantly reduced survival. Altogether, these data highlight important roles for FA and ketone body metabolism that could serve to improve targeted therapies in GBM.Competing Interest StatementThe authors have declared no competing interest.