title: Influence of Serum and Hypoxia on Incorporation of [(14)C]-D-Glucose or [(14)C]-L-Glutamine into Lipids and Lactate in Murine Glioblastoma Cells.
abstract: Glucose and glutamine are essential energy metabolites for brain tumor growth and survival under both normoxic and hypoxic conditions. Both metabolites can contribute their carbons to lipid biosynthesis. We used uniformly labeled [(14)C]-U-D-glucose and [(14)C]-U-L-glutamine to examine the profile of de novo lipid biosynthesis in the VM-M3 murine glioblastoma cells. The major lipids synthesized included phosphatidylcholine (PtdCho), phosphatidylethanolamine (EtnGpl), phosphatidylinositol (PtdIns), phosphatidylserine (PtdSer), sphingomyelin (CerPCho), bis(monoacylglycero)phosphate (BMP)/phosphatidic acid (PtdOH), cholesterol (C), cardiolipin (Ptd2Gro), and gangliosides. Endogenous lipid synthesis, using either glucose or glutamine, was greater in media without fetal bovine serum (FBS) than in media containing 10 % FBS under normoxia. De novo lipid synthesis was greater using glucose carbons than glutamine carbons under normoxia. The reverse was observed for most lipids under hypoxia suggesting an attenuation of glucose entering the TCA cycle. Lactate was produced largely from glucose carbons with minimal lactate derived from glutamine under either normoxia or hypoxia. Accumulation of triacylglycerols (TAG), containing mostly saturated and mono-unsaturated fatty acids, was observed under hypoxia using carbons from either glucose or glutamine. The data show that the incorporation of labeled glucose and glutamine into most synthesized lipids was dependent on the type of growth environment, and that the VM-M3 glioblastoma cells could acquire lipids, especially cholesterol, from the external environment for growth and proliferation.
authors.affiliation: Biology Department, Boston College, Chestnut Hill, Boston, MA, 02467, USA. tali@bc.edu.
authors.forename: Nathan L
authors.initials: NL
authors.lastname: Ta
authors.affiliation: Biology Department, Boston College, Chestnut Hill, Boston, MA, 02467, USA. thomas.seyfried@bc.edu.
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Seyfried
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes; D002417:Cattle; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002784:Cholesterol / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005732:Gangliosides / Q000378:metabolism; D005909:Glioblastoma / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism*; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D010743:Phospholipids / Q000378:metabolism; D044967:Serum / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D002250:Carbon Radioisotopes; D005227:Fatty Acids; D005732:Gangliosides; D010743:Phospholipids; D014280:Triglycerides; D005973:Glutamine; D019344:Lactic Acid; D002784:Cholesterol; D005947:Glucose
keywords: Analytical techniques GLC (GC) (gas-liquid chromatography); Analytical techniques, lipid biochemistry; Analytical techniques, radiotracer; Analytical techniques, thin layer chromatography; Analytical techniques, triglyceride analysis; Energy metabolism; Fatty acid analysis; General area, lipogenesis; Glioblastoma; Hypoxia