Exogenous Fatty Acids Are the Preferred Source of Membrane Lipids in Proliferating Fibroblasts

Cong Hui Yao, Ronald Fowle-Grider, Nathanial G. Mahieu, Gao Yuan Liu, Ying Jr Chen, Rencheng Wang, Manmilan Singh, Gregory S. Potter, Richard W. Gross, Jacob Schaefer, Stephen L. Johnson, Gary J. Patti

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Cellular proliferation requires the formation of new membranes. It is often assumed that the lipids needed for these membranes are synthesized mostly de novo. Here, we show that proliferating fibroblasts prefer to take up palmitate from the extracellular environment over synthesizing it de novo. Relative to quiescent fibroblasts, proliferating fibroblasts increase their uptake of palmitate, decrease fatty acid degradation, and instead direct more palmitate to membrane lipids. When exogenous palmitate is provided in the culture media at physiological concentrations, de novo synthesis accounts for only a minor fraction of intracellular palmitate in proliferating fibroblasts as well as proliferating HeLa and H460 cells. Blocking fatty acid uptake decreased the proliferation rate of fibroblasts, HeLa, and H460 cells, while supplementing media with exogenous palmitate resulted in decreased glucose uptake and rendered cells less sensitive to glycolytic inhibition. Our results suggest that cells scavenging exogenous lipids may be less susceptible to drugs targeting glycolysis and de novo lipid synthesis.

Original languageEnglish
Pages (from-to)483-493
Number of pages11
JournalCell Chemical Biology
Volume23
Issue number4
DOIs
StatePublished - Apr 21 2016

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    Yao, C. H., Fowle-Grider, R., Mahieu, N. G., Liu, G. Y., Chen, Y. J., Wang, R., Singh, M., Potter, G. S., Gross, R. W., Schaefer, J., Johnson, S. L., & Patti, G. J. (2016). Exogenous Fatty Acids Are the Preferred Source of Membrane Lipids in Proliferating Fibroblasts. Cell Chemical Biology, 23(4), 483-493. https://doi.org/10.1016/j.chembiol.2016.03.007