title: Exogenous Fatty Acids Are the Preferred Source of Membrane Lipids in Proliferating Fibroblasts.
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.
authors.affiliation: Department of Chemistry, Washington University, St. Louis, MO 63130, USA; Department of Medicine, Washington University, St. Louis, MO 63110, USA.
authors.forename: Cong-Hui
authors.initials: CH
authors.lastname: Yao
authors.affiliation: Department of Chemistry, Washington University, St. Louis, MO 63130, USA; Department of Medicine, Washington University, St. Louis, MO 63110, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Fowle-Grider
authors.affiliation: Department of Chemistry, Washington University, St. Louis, MO 63130, USA; Department of Medicine, Washington University, St. Louis, MO 63110, USA.
authors.forename: Nathanial G
authors.initials: NG
authors.lastname: Mahieu
authors.affiliation: Department of Chemistry, Washington University, St. Louis, MO 63130, USA; Division of Bioorganic and Molecular Pharmacology, Department of Internal Medicine, Washington University, St. Louis, MO 63110, USA.
authors.forename: Gao-Yuan
authors.initials: GY
authors.lastname: Liu
authors.affiliation: Department of Chemistry, Washington University, St. Louis, MO 63130, USA; Department of Medicine, Washington University, St. Louis, MO 63110, USA.
authors.forename: Ying-Jr
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Department of Chemistry, Washington University, St. Louis, MO 63130, USA; Department of Medicine, Washington University, St. Louis, MO 63110, USA; Department of Genetics, Washington University, St. Louis, MO 63110, USA.
authors.forename: Rencheng
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Chemistry, Washington University, St. Louis, MO 63130, USA.
authors.forename: Manmilan
authors.initials: M
authors.lastname: Singh
authors.affiliation: Department of Chemistry, Washington University, St. Louis, MO 63130, USA.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Potter
authors.affiliation: Department of Chemistry, Washington University, St. Louis, MO 63130, USA; Division of Bioorganic and Molecular Pharmacology, Department of Internal Medicine, Washington University, St. Louis, MO 63110, USA.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Gross
authors.affiliation: Department of Chemistry, Washington University, St. Louis, MO 63130, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Schaefer
authors.affiliation: Department of Genetics, Washington University, St. Louis, MO 63110, USA.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Johnson
authors.affiliation: Department of Chemistry, Washington University, St. Louis, MO 63130, USA; Department of Medicine, Washington University, St. Louis, MO 63110, USA. Electronic address: gjpattij@wustl.edu.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Patti
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005227:Fatty Acids / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism*; D051379:Mice
chemical_list: D005227:Fatty Acids; D008563:Membrane Lipids