Characterization of glucose-related metabolic pathways in differentiated rat oligodendrocyte lineage cells
Porem Amaral, Ana Amaral
Hadera, Mussie G
Tavares, Joana M
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Porem Amaral, A. A., Hadera, M. G., Tavares, J. M., Kotter, M., & Sonnewald, U. (2015). Characterization of glucose-related metabolic pathways in differentiated rat oligodendrocyte lineage cells. Glia, 64 21-34. https://doi.org/10.1002/glia.22900
Although oligodendrocytes constitute a significant proportion of cells in the central nervous system (CNS), little is known about their intermediary metabolism. We have therefore characterised 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 metabolise glucose in the cytosol and pyruvate derived from glucose in the mitochondria. The labelling patterns of metabolites obtained after incubation with [1,2-13C]glucose demonstrated that the pentose phosphate pathway (PPP) is highly active in oligodendrocytes (approximately 10% of glucose is metabolised via the PPP as indicated by labelling patterns in phosphoenolpyruvate). Mass spectrometry and magnetic resonance spectroscopy analyses of metabolites after incubation of cells with [1-13C]lactate or [1,2-13C]glucose, respectively, demonstrated that anaplerotic pyruvate carboxylation, which was thought to be exclusive to astrocytes, is also active in oligodendrocytes. Using [1,2-13C]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 [1,2-13C]acetate and [1,2-13C]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.
Oligodendroglia, energy, metabolism, glucose, 13C, mitochondria, glycolysis, acetate, pyruvate carboxylation
Grant sponsor: The UK Multiple Sclerosis Society and Qatar Foundation. The work was further supported by core funding from the Wellcome Trust and MRC to the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute.
External DOI: https://doi.org/10.1002/glia.22900
This record's URL: https://www.repository.cam.ac.uk/handle/1810/250443
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/