Characterization of glucose-related metabolic pathways in differentiated rat oligodendrocyte lineage cells.
Although oligodendrocytes constitute a significant proportion of cells in the central nervous system (CNS), little is known about their intermediary metabolism. We have, therefore, characterized metabolic functions of primary oligodendrocyte precursor cell cultures at late stages of differentiation using isotope-labelled metabolites. We report that differentiated oligodendrocyte lineage cells avidly metabolize glucose in the cytosol and pyruvate derived from glucose in the mitochondria. The labelling patterns of metabolites obtained after incubation with [1,2-(13)C]glucose demonstrated that the pentose phosphate pathway (PPP) is highly active in oligodendrocytes (approximately 10% of glucose is metabolized via the PPP as indicated by labelling patterns in phosphoenolpyruvate). Mass spectrometry and magnetic resonance spectroscopy analyses of metabolites after incubation of cells with [1-(13)C]lactate or [1,2-(13)C]glucose, respectively, demonstrated that anaplerotic pyruvate carboxylation, which was thought to be exclusive to astrocytes, is also active in oligodendrocytes. Using [1,2-(13)C]acetate, we show that oligodendrocytes convert acetate into acetyl CoA which is metabolized in the tricarboxylic acid cycle. Analysis of labelling patterns of alanine after incubation of cells with [1,2-(13)C]acetate and [1,2-(13)C]glucose showed catabolic oxidation of malate or oxaloacetate. In conclusion, we report that oligodendrocyte lineage cells at late differentiation stages are metabolically highly active cells that are likely to contribute considerably to the metabolic activity of the CNS.
Anne McLaren Laboratory, Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute and Department of Clinical Neurosciences, University of Cambridge, Cambridge, CB2 0SZ, United Kingdom.
Ana I
AI
Amaral
Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, 7491, Norway.
Mussie G
MG
Hadera
Anne McLaren Laboratory, Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute and Department of Clinical Neurosciences, University of Cambridge, Cambridge, CB2 0SZ, United Kingdom.
Joana M
JM
Tavares
Anne McLaren Laboratory, Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute and Department of Clinical Neurosciences, University of Cambridge, Cambridge, CB2 0SZ, United Kingdom.
Mark R N
MR
Kotter
Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, 7491, Norway.|Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2100, Denmark.
Ursula
U
Sonnewald
D000085:Acetates / Q000378:metabolism; D000105:Acetyl Coenzyme A / Q000378:metabolism; D000818:Animals; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D002952:Citric Acid Cycle / Q000502:physiology; D003600:Cytosol / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism; D008293:Malates / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism*; D062907:Oxaloacetic Acid / Q000378:metabolism; D010427:Pentose Phosphate Pathway / Q000502:physiology; D010728:Phosphoenolpyruvate / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism; D019275:Radiopharmaceuticals; D017207:Rats, Sprague-Dawley
D000085:Acetates; D002250:Carbon Radioisotopes; D008293:Malates; D019275:Radiopharmaceuticals; D062907:Oxaloacetic Acid; D019344:Lactic Acid; D000105:Acetyl Coenzyme A; D010728:Phosphoenolpyruvate; C030298:malic acid; D019289:Pyruvic Acid; D005947:Glucose
13C; acetate; energy metabolism; glucose; glycolysis; mitochondria; oligodendroglia; pyruvate carboxylation