Exogenous Fatty Acids Are the Preferred Source of Membrane Lipids in Proliferating Fibroblasts. Issue 4 (21st April 2016)

• Record Type: Journal Article
• Authors: Yao, Cong-Hui; Fowle-Grider, Ronald; Mahieu, Nathanial G.; Liu, Gao-Yuan; Chen, Ying-Jr; Wang, Rencheng; Singh, Manmilan; Potter, Gregory S.; Gross, Richard W.; Schaefer, Jacob; Johnson, Stephen L.; Patti, Gary J.
• Is Part Of: Cell chemical biology. Volume 23:Issue 4(2016)
• Page Start: 483
• Page End: 493
• Publication Date: 2016-04-21
• Subjects: Biochemistry -- Periodicals; 572.05
• DOI: 10.1016/j.chembiol.2016.03.007
• Languages: English
• ISSNs: 2451-9456

Abstract

Summary: 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. Graphical Abstract: Highlights: Exogenous palmitate is preferred over de novo synthesis for three cell lines Proliferating fibroblasts decrease β-oxidation to support complex-lipid synthesis Glutamine does not contribute more carbon to lipids in proliferating fibroblasts An inhibitor of fatty acid uptake decreases cellular proliferation in three cell lines Abstract : Non-lipid nutrients have been the most studied source of lipids in proliferating cells. Yao et al. show that proliferating fibroblasts, HeLa, and H460 cells prefer to take up lipids from the extracellular environment directly rather than synthesize them de novo .