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Abstract
Metabolic rewiring fuels tumorigenicity of cancer stem cells contributing to universal glioblastoma (GBM) recurrence. Invasive glioblastoma stem cells (GSCs), already unresectable, acquire tumorigenic properties that confer therapy resistance. Using samples from both recurrent and newly diagnosed GBM patients, we identified fatty acid oxidation (FAO) as a key pathway supporting GSC tumorigenicity. Transcriptomic profiling, compared against non-malignant human astrocytes from epilepsy patients, highlighted an FAO-enriched signature in GSCs. In vivo studies showed that tumor formation by these GSCs could be modulated by altering the availability of metabolizable lipids in the brain, with beneficial effects observed under a low carbohydrate high fat diet (LCHFD). The lipid metabolism contributing to GSC mediated tumor formation was confirmed using metabolomic and lipidomic analyses. Gut microbiome analyses revealed that LCHFD shapes the microbiome and modulates the circadian network. By targeting FAO in the postoperative period before chemoradiation, LCHFD offers a non-pharmacologic strategy to delay GBM recurrence. This study suggests a mechanistic framework for dietary modulation as a therapeutic approach to improve GBM outcomes.
Acknowledgements
We thank Dr. Akil Kalathil for technical help during one of our in vivo studies and Dr. Eva M. Medina-Rodriguez for one of our neurobehavior analyses studies
Funding
S.D. discloses support for the research of this work from Florida Department of Health Casey DeSantis Florida Cancer Innovation Fund (25C44), and bridge funding from Sylvester Comprehensive Cancer Center. We also thank Sylvester Comprehensive Cancer Center, the NCI funded Sylvester Comprehensive Cancer Center support grant 1P30CA240139. We thank the Cancer Modeling Shared Re, and NIH grant 1S10OD023579-01 for the VS120 Slide Scanner
Author notes
These authors contributed equally: Shrita Sarkar, Akash Ashokan, Bapurao Surnar
Authors and Affiliations
Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, FL, USA
Shrita Sarkar, Akash Ashokan, Bapurao Surnar, Bhabatosh Banik, Daniel C. Bilbao, Eléonore Beurel & Shanta Dhar
Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, USA
Akash Ashokan, Stefano Lepore, Ricardo J. Komotar, Daniel C. Bilbao, Michael E. Ivan & Shanta Dhar
Department of Neurological Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA
Daniel G. Eichberg, Tatiana I. Slepak, Ricardo J. Komotar & Michael E. Ivan
Department of Biochemistry and Molecular Pharmacology, NYU Langone Medical Center, New York, NY, USA
Lia Ficaro & Drew R. Jones
Department of Pathology and Laboratory Medicine, University of Miami School of Medicine, Miami, FL, USA
Daniel C. Bilbao
Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL, USA
Eléonore Beurel
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Sarkar, S., Ashokan, A., Surnar, B. et al. Low carbohydrate high fat diet curbs glioblastoma by shifting lipids and limiting cancer stem cell metabolic flexibility.
Commun Biol (2026). https://doi.org/10.1038/s42003-026-10516-1
Received:30 September 2025
Accepted:10 June 2026
Published:27 July 2026
DOI
:https://doi.org/10.1038/s42003-026-10516-1
