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Lipid accumulation and oxidation in glioblastoma multiforme

Glioblastoma multiforme (GBM) is the most common and lethal primary malignant brain tumor in adults. Despite the multimodal standard treatments for GBM, the median survival is still about one year. Analysis of brain tissues from GBM patients shows that lipid droplets are highly enriched in tumor tis...

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Autores principales: Taïb, Bouchra, Aboussalah, Amine M., Moniruzzaman, Mohammed, Chen, Suming, Haughey, Norman J., Kim, Sangwon F., Ahima, Rexford S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925201/
https://www.ncbi.nlm.nih.gov/pubmed/31863022
http://dx.doi.org/10.1038/s41598-019-55985-z
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author Taïb, Bouchra
Aboussalah, Amine M.
Moniruzzaman, Mohammed
Chen, Suming
Haughey, Norman J.
Kim, Sangwon F.
Ahima, Rexford S.
author_facet Taïb, Bouchra
Aboussalah, Amine M.
Moniruzzaman, Mohammed
Chen, Suming
Haughey, Norman J.
Kim, Sangwon F.
Ahima, Rexford S.
author_sort Taïb, Bouchra
collection PubMed
description Glioblastoma multiforme (GBM) is the most common and lethal primary malignant brain tumor in adults. Despite the multimodal standard treatments for GBM, the median survival is still about one year. Analysis of brain tissues from GBM patients shows that lipid droplets are highly enriched in tumor tissues while undetectable in normal brain tissues, yet the identity and functions of lipid species in GBM are not well understood. The aims of the present work are to determine how GBM utilizes fatty acids, and assess their roles in GBM proliferation. Treatment of U138 GBM cells with a monounsaturated fatty acid, oleic acid, induces accumulation of perilipin 2-coated lipid droplets containing triglycerides enriched in C18:1 fatty acid, and increases fatty acid oxidation. Interestingly, oleic acid also increases glucose utilization and proliferation of GBM cells. In contrast, pharmacologic inhibition of monoacylglycerol lipase attenuates GBM proliferation. Our findings demonstrate that monounsaturated fatty acids promote GBM proliferation via triglyceride metabolism, suggesting a novel lipid droplet-mediated pathway which may be targeted for GBM treatment.
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spelling pubmed-69252012019-12-24 Lipid accumulation and oxidation in glioblastoma multiforme Taïb, Bouchra Aboussalah, Amine M. Moniruzzaman, Mohammed Chen, Suming Haughey, Norman J. Kim, Sangwon F. Ahima, Rexford S. Sci Rep Article Glioblastoma multiforme (GBM) is the most common and lethal primary malignant brain tumor in adults. Despite the multimodal standard treatments for GBM, the median survival is still about one year. Analysis of brain tissues from GBM patients shows that lipid droplets are highly enriched in tumor tissues while undetectable in normal brain tissues, yet the identity and functions of lipid species in GBM are not well understood. The aims of the present work are to determine how GBM utilizes fatty acids, and assess their roles in GBM proliferation. Treatment of U138 GBM cells with a monounsaturated fatty acid, oleic acid, induces accumulation of perilipin 2-coated lipid droplets containing triglycerides enriched in C18:1 fatty acid, and increases fatty acid oxidation. Interestingly, oleic acid also increases glucose utilization and proliferation of GBM cells. In contrast, pharmacologic inhibition of monoacylglycerol lipase attenuates GBM proliferation. Our findings demonstrate that monounsaturated fatty acids promote GBM proliferation via triglyceride metabolism, suggesting a novel lipid droplet-mediated pathway which may be targeted for GBM treatment. Nature Publishing Group UK 2019-12-20 /pmc/articles/PMC6925201/ /pubmed/31863022 http://dx.doi.org/10.1038/s41598-019-55985-z Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Taïb, Bouchra
Aboussalah, Amine M.
Moniruzzaman, Mohammed
Chen, Suming
Haughey, Norman J.
Kim, Sangwon F.
Ahima, Rexford S.
Lipid accumulation and oxidation in glioblastoma multiforme
title Lipid accumulation and oxidation in glioblastoma multiforme
title_full Lipid accumulation and oxidation in glioblastoma multiforme
title_fullStr Lipid accumulation and oxidation in glioblastoma multiforme
title_full_unstemmed Lipid accumulation and oxidation in glioblastoma multiforme
title_short Lipid accumulation and oxidation in glioblastoma multiforme
title_sort lipid accumulation and oxidation in glioblastoma multiforme
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925201/
https://www.ncbi.nlm.nih.gov/pubmed/31863022
http://dx.doi.org/10.1038/s41598-019-55985-z
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