Glioblastoma Utilizes Fatty Acids and Ketone Bodies for Growth Allowing Progression during Ketogenic Diet Therapy
Summary: 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...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-09-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004220306453 |
| id |
doaj-c408bc708ce74fd297a8a89e0dcb76f3 |
|---|---|
| record_format |
Article |
| spelling |
doaj-c408bc708ce74fd297a8a89e0dcb76f32020-11-25T02:51:20ZengElsevieriScience2589-00422020-09-01239101453Glioblastoma Utilizes Fatty Acids and Ketone Bodies for Growth Allowing Progression during Ketogenic Diet TherapyJantzen Sperry0Michael C. Condro1Lea Guo2Daniel Braas3Nathan Vanderveer-Harris4Kristen K.O. Kim5Whitney B. Pope6Ajit S. Divakaruni7Albert Lai8Heather Christofk9Maria G. Castro10Pedro R. Lowenstein11Janel E. Le Belle12Harley I. Kornblum13Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USADepartment of Psychiatry and Biobehavioral Sciences and Semel Institute for Neuroscience & Human Behavior, UCLA, Los Angeles, CA, USADepartment of Psychiatry and Biobehavioral Sciences and Semel Institute for Neuroscience & Human Behavior, UCLA, Los Angeles, CA, USA; Department of Radiological Sciences, David Geffen School of Medicine, UCLA, Los Angeles, CA, USAUCLA Metabolomics Center, UCLA, Los Angeles, CA, USADepartment of Psychiatry and Biobehavioral Sciences and Semel Institute for Neuroscience & Human Behavior, UCLA, Los Angeles, CA, USADepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USADepartment of Radiological Sciences, David Geffen School of Medicine, UCLA, Los Angeles, CA, USADepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USAJonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, USA; Department of Neurology, UCLA, Los Angeles, CA, USADepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, USA; Department of Biological Chemistry, UCLA, Los Angeles, CA, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA, USADepartment of Neurosurgery, Department of Cell and Developmental Biology, Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USADepartment of Neurosurgery, Department of Cell and Developmental Biology, Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USADepartment of Psychiatry and Biobehavioral Sciences and Semel Institute for Neuroscience & Human Behavior, UCLA, Los Angeles, CA, USADepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; Department of Psychiatry and Biobehavioral Sciences and Semel Institute for Neuroscience & Human Behavior, UCLA, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004220306453PathophysiologyCancerDiet |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Jantzen Sperry Michael C. Condro Lea Guo Daniel Braas Nathan Vanderveer-Harris Kristen K.O. Kim Whitney B. Pope Ajit S. Divakaruni Albert Lai Heather Christofk Maria G. Castro Pedro R. Lowenstein Janel E. Le Belle Harley I. Kornblum |
| spellingShingle |
Jantzen Sperry Michael C. Condro Lea Guo Daniel Braas Nathan Vanderveer-Harris Kristen K.O. Kim Whitney B. Pope Ajit S. Divakaruni Albert Lai Heather Christofk Maria G. Castro Pedro R. Lowenstein Janel E. Le Belle Harley I. Kornblum Glioblastoma Utilizes Fatty Acids and Ketone Bodies for Growth Allowing Progression during Ketogenic Diet Therapy iScience Pathophysiology Cancer Diet |
| author_facet |
Jantzen Sperry Michael C. Condro Lea Guo Daniel Braas Nathan Vanderveer-Harris Kristen K.O. Kim Whitney B. Pope Ajit S. Divakaruni Albert Lai Heather Christofk Maria G. Castro Pedro R. Lowenstein Janel E. Le Belle Harley I. Kornblum |
| author_sort |
Jantzen Sperry |
| title |
Glioblastoma Utilizes Fatty Acids and Ketone Bodies for Growth Allowing Progression during Ketogenic Diet Therapy |
| title_short |
Glioblastoma Utilizes Fatty Acids and Ketone Bodies for Growth Allowing Progression during Ketogenic Diet Therapy |
| title_full |
Glioblastoma Utilizes Fatty Acids and Ketone Bodies for Growth Allowing Progression during Ketogenic Diet Therapy |
| title_fullStr |
Glioblastoma Utilizes Fatty Acids and Ketone Bodies for Growth Allowing Progression during Ketogenic Diet Therapy |
| title_full_unstemmed |
Glioblastoma Utilizes Fatty Acids and Ketone Bodies for Growth Allowing Progression during Ketogenic Diet Therapy |
| title_sort |
glioblastoma utilizes fatty acids and ketone bodies for growth allowing progression during ketogenic diet therapy |
| publisher |
Elsevier |
| series |
iScience |
| issn |
2589-0042 |
| publishDate |
2020-09-01 |
| description |
Summary: 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. |
| topic |
Pathophysiology Cancer Diet |
| url |
http://www.sciencedirect.com/science/article/pii/S2589004220306453 |
| work_keys_str_mv |
AT jantzensperry glioblastomautilizesfattyacidsandketonebodiesforgrowthallowingprogressionduringketogenicdiettherapy AT michaelccondro glioblastomautilizesfattyacidsandketonebodiesforgrowthallowingprogressionduringketogenicdiettherapy AT leaguo glioblastomautilizesfattyacidsandketonebodiesforgrowthallowingprogressionduringketogenicdiettherapy AT danielbraas glioblastomautilizesfattyacidsandketonebodiesforgrowthallowingprogressionduringketogenicdiettherapy AT nathanvanderveerharris glioblastomautilizesfattyacidsandketonebodiesforgrowthallowingprogressionduringketogenicdiettherapy AT kristenkokim glioblastomautilizesfattyacidsandketonebodiesforgrowthallowingprogressionduringketogenicdiettherapy AT whitneybpope glioblastomautilizesfattyacidsandketonebodiesforgrowthallowingprogressionduringketogenicdiettherapy AT ajitsdivakaruni glioblastomautilizesfattyacidsandketonebodiesforgrowthallowingprogressionduringketogenicdiettherapy AT albertlai glioblastomautilizesfattyacidsandketonebodiesforgrowthallowingprogressionduringketogenicdiettherapy AT heatherchristofk glioblastomautilizesfattyacidsandketonebodiesforgrowthallowingprogressionduringketogenicdiettherapy AT mariagcastro glioblastomautilizesfattyacidsandketonebodiesforgrowthallowingprogressionduringketogenicdiettherapy AT pedrorlowenstein glioblastomautilizesfattyacidsandketonebodiesforgrowthallowingprogressionduringketogenicdiettherapy AT janelelebelle glioblastomautilizesfattyacidsandketonebodiesforgrowthallowingprogressionduringketogenicdiettherapy AT harleyikornblum glioblastomautilizesfattyacidsandketonebodiesforgrowthallowingprogressionduringketogenicdiettherapy |
| _version_ |
1724735187710902272 |