Plasma lipidomic and metabolomic profiles in high-grade glioma patients before and after 72-h presurgery water-only fasting

Glioblastoma (GB) is the most aggressive primary brain tumor with poor prognosis despite multimodal therapy. Calorie-restricted diets have emerged as putative strategies to augment anticancer therapies. We employed UHPLC-high-resolution mass spectrometry analyses of plasma lipids and polar metabolites to assess the systemic metabolic effects of a 72-h preoperative fasting period in IDH-wild-type glioma patients (n = 9 GB and n = 1 diffuse pediatric-type high-grade H3/IDH-wildtype) who participated in the prospective ERGO3 trial (NCT04461938). Fasting reduced lysophosphatidylcholines (LPC, LPC-O), lysophosphatidylethanolamines (LPE, LPE-O), and increased free fatty acids and carnitines. Triglyceride (TG) profiles shifted from short-chain TGs (42-48 C-atoms) to very long-chain TGs (58-60 C-atoms) indicating an exploitation of neutral lipid stores. Branched-chain amino acids, aminobutyric acid, and uric acids were increased, and glucose reduced after fasting. The effects of fasting were comparable in men and women. To our knowledge, this is the first study that evaluated the effects of fasting on systemic lipid/metabolite levels in GB patients. Our results may hold promise for integrating fasting interventions as a component of a potential metabolic tumor therapy.