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Publication : A Fatty Acid Oxidation-Dependent Metabolic Shift Regulates Adult Neural Stem Cell Activity.

First Author  Knobloch M Year  2017
Journal  Cell Rep Volume  20
Issue  9 Pages  2144-2155
PubMed ID  28854364 Mgi Jnum  J:250027
Mgi Id  MGI:6099413 Doi  10.1016/j.celrep.2017.08.029
Citation  Knobloch M, et al. (2017) A Fatty Acid Oxidation-Dependent Metabolic Shift Regulates Adult Neural Stem Cell Activity. Cell Rep 20(9):2144-2155
abstractText  Hippocampal neurogenesis is important for certain forms of cognition, and failing neurogenesis has been implicated in neuropsychiatric diseases. The neurogenic capacity of hippocampal neural stem/progenitor cells (NSPCs) depends on a balance between quiescent and proliferative states. Here, we show that the rate of fatty acid oxidation (FAO) regulates the activity of NSPCs. Quiescent NSPCs show high levels of carnitine palmitoyltransferase 1a (Cpt1a)-dependent FAO, which is downregulated in proliferating NSPCs. Pharmacological inhibition and conditional deletion of Cpt1a in vitro and in vivo leads to altered NSPC behavior, showing that Cpt1a-dependent FAO is required for stem cell maintenance and proper neurogenesis. Strikingly, manipulation of malonyl-CoA, the metabolite that regulates levels of FAO, is sufficient to induce exit from quiescence and to enhance NSPC proliferation. Thus, the data presented here identify a shift in FAO metabolism that governs NSPC behavior and suggest an instructive role for fatty acid metabolism in regulating NSPC activity.
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