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Influence of serum and hypoxia on endogenously synthesized lipids and lactate from radiolabeled glucose or glutamine in murine glioblastoma cells
Author(s) -
Ta Nathan,
Seyfried Thomas
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.568.16
Subject(s) - glutamine , biochemistry , de novo synthesis , metabolism , hypoxia (environmental) , biosynthesis , cholesterol , chemistry , biology , amino acid , enzyme , oxygen , organic chemistry
Glucose and glutamine are essential energy metabolites for brain tumor growth and survival under both normoxic and hypoxic conditions. These metabolic substrates contribute their carbons to lipid biosynthesis. We used uniformly labeled [ 14 C]‐U‐D‐glucose and [ 14 C]‐U‐L‐glutamine to examine the de novo biosynthesis of all major phospholipids, cholesterol, and gangliosides in the VM‐M3 murine glioblastoma cells. 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, containing mostly saturated and mono‐unsaturated fatty acids, was observed under hypoxia using carbons from either glucose or glutamine. The incorporation of labeled glucose and glutamine into most synthesized lipids was dependent on the type of growth environment, and that the VM‐M3 cells could acquire lipids, especially cholesterol, from the external environment for growth and proliferation. These results can help clarify the origin of lactate synthesis and the role of exogenous lipids, acquired from the microenvironment, in driving tumor cell growth.