Integrated Metabolomics and Lipidomics Analyses Reveal Metabolic Reprogramming in Human Glioma with IDH1 Mutation

Mutations
in isocitrate dehydrogenase (IDH) 1
are high-frequency events in low-grade glioma and secondary glioblastoma,
and IDH1 mutant gliomas are vulnerable to interventions.
Metabolic reprogramming is a hallmark of cancer. In this study, comprehensive
metabolism investigation of clinical IDH1 mutant
glioma specimens was performed to explore its specific metabolic reprogramming
in real microenvironment. Massive metabolic alterations from glycolysis
to lipid metabolism were identified in the IDH1 mutant
glioma tissue when compared to IDH1 wild-type glioma.
Of note, tricarboxylic acid (TCA) cycle intermediates were in similar
levels in both groups, with more pyruvate found entering the TCA cycle
in IDH1 mutant glioma. The pool of fatty acyl chains
was also reduced, displayed as decreased triglycerides and sphingolipids,
although membrane phosphatidyl lipids were not changed. The lower
fatty acyl pool may be mediated by the lower protein expression levels
of long-chain acyl-CoA synthetase 1 (ACSL1), ACSL4, and very long-chain
acyl-CoA synthetase 3 (ACSVL3) in IDH1 mutant glioma.
Lower ACSL1 was further found to contribute to the better survival
of IDH1 mutant glioma patients based on the The Cancer
Genome Atlas (TCGA) RNA sequencing data. Our research provides valuable
insights into the tissue metabolism of human IDH1 mutant glioma and unravels new lipid-related targets.