In vivo metabolism of glucose and acetate in human meningiomas: A 13C NMR-based metabolic flux analysis

Motivation: Metabolism plays a key role in the growth and proliferation of brain tumors including aggressive meningiomas. We previously reported that meningiomas preferentially utilize acetate as a bioenergetic substrate. However, the metabolism of acetate in the presence of glucose is not well understood. Goal(s): To investigate the simultaneous in vivo metabolism of acetate and glucose in meningiomas. Approach: We infused [2-13C]acetate and [U-13C]glucose as metabolic tracers in meningioma patients to determine the relative utilization of both nutrients by meningiomas. Results: Grade-II meningiomas utilize relatively less amount of glucose (grade-II: 0.6% vs. grade-I: ~5.4%) and more acetate than grade-I meningiomas (grade-II: 45.8% vs. grade-I: ~31.24%). Impact: No chemotherapy is available for the treatment of meningiomas. The findings from this study will be helpful in designing targeted metabolic therapy for aggressive meningiomas using small molecule inhibitors (e.g., ACSS2 inhibitor) involved in acetate metabolism.