The Effect of Unsaturated Fatty Acids on the Growth, Metabolism and Productivity of a Murine Hybridoma
Abstract
Supplementation of linoleic acid or oleic acid (10-50 µM) improved the cell yield of a murine hybridoma (CC9C10) grown in serum-free media. The maximal cell yield was obtained in an oleic/ linoleic mix (25 AM). The fatty acids also caused a significant increase (78%) in the volumetric Mab titre. However, continued growth of the cells in the fatty acid supplemented media over several passages resulted in a gradual deterioration of the Mab yield concomitant with the appearance of lipid inclusions in the cytosol. Incorporation studies with14C-linoleic acid showed the distribution of the fatty acid into cell fractions was as follows: polar lipid (80%), non-polar lipid (16%) and free fatty acid (4%). The metabolic effects of the fatty acid addition were studied by measurements of rates of oxidation of radioactively labelled substrates. Cells grown in fatty acids showed significant changes in energy metabolism with a decreased (x2) rate of oxidation of glutamine and an increased (x3) rate of oxidation of glucose. The flux of glucose through all three measured metabolic pathways (glycolysis, pentose phosphate pathway and TCA cycle) was enhanced in cells grown in fatty acids.
Keywords
Free Fatty Acid Linoleic Acid Unsaturated Fatty Acid Polar Lipid Lipid InclusionPreview
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