PMID- 32861192
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230816
IS  - 2589-0042 (Electronic)
IS  - 2589-0042 (Linking)
VI  - 23
IP  - 9
DP  - 2020 Sep 25
TI  - Glioblastoma Utilizes Fatty Acids and Ketone Bodies for Growth Allowing 
      Progression during Ketogenic Diet Therapy.
PG  - 101453
LID - 10.1016/j.isci.2020.101453 [doi]
LID - 101453
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.
CI  - (c) 2020 The Authors.
FAU - Sperry, Jantzen
AU  - Sperry J
AD  - Department of Molecular and Medical Pharmacology, David Geffen School of 
      Medicine, University of California, Los Angeles, CA 90095, USA.
FAU - Condro, Michael C
AU  - Condro MC
AD  - Department of Psychiatry and Biobehavioral Sciences and Semel Institute for 
      Neuroscience & Human Behavior, UCLA, Los Angeles, CA, USA.
FAU - Guo, Lea
AU  - Guo L
AD  - Department of Psychiatry and Biobehavioral Sciences and Semel Institute for 
      Neuroscience & Human Behavior, UCLA, Los Angeles, CA, USA.
AD  - Department of Radiological Sciences, David Geffen School of Medicine, UCLA, Los 
      Angeles, CA, USA.
FAU - Braas, Daniel
AU  - Braas D
AD  - UCLA Metabolomics Center, UCLA, Los Angeles, CA, USA.
FAU - Vanderveer-Harris, Nathan
AU  - Vanderveer-Harris N
AD  - Department of Psychiatry and Biobehavioral Sciences and Semel Institute for 
      Neuroscience & Human Behavior, UCLA, Los Angeles, CA, USA.
FAU - Kim, Kristen K O
AU  - Kim KKO
AD  - Department of Molecular and Medical Pharmacology, David Geffen School of 
      Medicine, University of California, Los Angeles, CA 90095, USA.
FAU - Pope, Whitney B
AU  - Pope WB
AD  - Department of Radiological Sciences, David Geffen School of Medicine, UCLA, Los 
      Angeles, CA, USA.
FAU - Divakaruni, Ajit S
AU  - Divakaruni AS
AD  - Department of Molecular and Medical Pharmacology, David Geffen School of 
      Medicine, University of California, Los Angeles, CA 90095, USA.
FAU - Lai, Albert
AU  - Lai A
AD  - Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, USA.
AD  - Department of Neurology, UCLA, Los Angeles, CA, USA.
FAU - Christofk, Heather
AU  - Christofk H
AD  - Department of Molecular and Medical Pharmacology, David Geffen School of 
      Medicine, University of California, Los Angeles, CA 90095, USA.
AD  - Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, USA.
AD  - Department of Biological Chemistry, UCLA, Los Angeles, CA, USA.
AD  - Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, 
      UCLA, Los Angeles, CA, USA.
FAU - Castro, Maria G
AU  - Castro MG
AD  - Department of Neurosurgery, Department of Cell and Developmental Biology, Rogel 
      Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
FAU - Lowenstein, Pedro R
AU  - Lowenstein PR
AD  - Department of Neurosurgery, Department of Cell and Developmental Biology, Rogel 
      Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
FAU - Le Belle, Janel E
AU  - Le Belle JE
AD  - Department of Psychiatry and Biobehavioral Sciences and Semel Institute for 
      Neuroscience & Human Behavior, UCLA, Los Angeles, CA, USA.
FAU - Kornblum, Harley I
AU  - Kornblum HI
AD  - Department of Molecular and Medical Pharmacology, David Geffen School of 
      Medicine, University of California, Los Angeles, CA 90095, USA.
AD  - Department of Psychiatry and Biobehavioral Sciences and Semel Institute for 
      Neuroscience & Human Behavior, UCLA, Los Angeles, CA, USA.
AD  - Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, USA.
AD  - Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, 
      UCLA, Los Angeles, CA, USA.
LA  - eng
GR  - P50 CA211015/CA/NCI NIH HHS/United States
GR  - R01 AR070245/AR/NIAMS NIH HHS/United States
GR  - R01 CA215185/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20200813
PL  - United States
TA  - iScience
JT  - iScience
JID - 101724038
PMC - PMC7471621
OTO - NOTNLM
OT  - Cancer
OT  - Diet
OT  - Pathophysiology
COIS- The authors declare no competing interests.
EDAT- 2020/08/30 06:00
MHDA- 2020/08/30 06:01
PMCR- 2020/08/13
CRDT- 2020/08/30 06:00
PHST- 2019/12/27 00:00 [received]
PHST- 2020/06/28 00:00 [revised]
PHST- 2020/08/10 00:00 [accepted]
PHST- 2020/08/30 06:01 [medline]
PHST- 2020/08/30 06:00 [pubmed]
PHST- 2020/08/30 06:00 [entrez]
PHST- 2020/08/13 00:00 [pmc-release]
AID - S2589-0042(20)30645-3 [pii]
AID - 101453 [pii]
AID - 10.1016/j.isci.2020.101453 [doi]
PST - epublish
SO  - iScience. 2020 Aug 13;23(9):101453. doi: 10.1016/j.isci.2020.101453. eCollection 
      2020 Sep 25.