Washington University in St. Louis

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Metabolomics to elucidate novel biochemical mechanisms of disease
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Exogenous Fatty Acids Are the Preferred Source of Membrane Lipids in Proliferating Fibroblasts

Yao C-H, Grider RF, Mahieu NG, Liu G-Y, Chen Y-J, Wang R, Singh M, Potter GS, Gross RW, Schaefer J, Johnson SL, Patti GJ
Exogenous Fatty Acids Are the Preferred Source of Membrane Lipids in Proliferating Fibroblasts
Cell Chemical Biology, 23, 1-11, 2016
10.1016/j.chembiol.2016.03.007
     Highlighted in Cell Chemical Biology 23, 431-432, 2016
     Liposuction: Extracellular Fat Removal Promotes Proliferation
     10.1016/j.chembiol.2016.04.003

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.

Washington University, Departments of Chemistry, Genetics, and Medicine. Saint Louis, Missouri 63110 USA