Acetate is a bioenergetic substrate for human glioblastoma and brain metastases

Tomoyuki Mashimo, Kumar Pichumani, Vamsidhara Vemireddy, Kimmo J. Hatanpaa, Dinesh Kumar Singh, Shyam Sirasanagandla, Suraj Nannepaga, Sara G. Piccirillo, Zoltan Kovacs, Chan Foong, Zhiguang Huang, Samuel Barnett, Bruce E. Mickey, Ralph J. Deberardinis, Benjamin P. Tu, Elizabeth A. Maher, Robert M. Bachoo

Research output: Contribution to journalArticlepeer-review

526 Scopus citations


Glioblastomas and brain metastases are highly proliferative brain tumors with short survival times. Previously, using 13C-NMR analysis of brain tumors resected from patients during infusion of 13C-glucose, we demonstrated that there is robust oxidation of glucose in the citric acid cycle, yet glucose contributes less than 50% of the carbons to the acetyl-CoA pool. Here, we show that primary and metastatic mouse orthotopic brain tumors have the capacity to oxidize [1,2-13C]acetate and can do so while simultaneously oxidizing [1,6-13C]glucose. The tumors do not oxidize [U-13C]glutamine. In vivo oxidation of [1,2-13C]acetate was validated in brain tumor patients and was correlated with expression of acetyl-CoA synthetase enzyme 2, ACSS2. Together, the data demonstrate a strikingly common metabolic phenotype in diverse brain tumors that includes the ability to oxidize acetate in the citric acid cycle. This adaptation may be important for meeting the high biosynthetic and bioenergetic demands of malignant growth.

Original languageEnglish (US)
Pages (from-to)1603-1614
Number of pages12
Issue number7
StatePublished - Dec 18 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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