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

Cell Rep. 2017 Aug 29;20(9):2144-2155. doi: 10.1016/j.celrep.2017.08.029.


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.

Keywords: beta-oxidation; hippocampus; metabolism; neural stem cell; neurogenesis; proliferation; quiescence.

MeSH terms

  • Animals
  • Carnitine O-Palmitoyltransferase / deficiency
  • Carnitine O-Palmitoyltransferase / metabolism
  • Cell Cycle
  • Cell Proliferation
  • Fatty Acids / metabolism*
  • Hippocampus / enzymology
  • Malonyl Coenzyme A / metabolism
  • Mice, Knockout
  • Neural Stem Cells / cytology
  • Neural Stem Cells / enzymology
  • Neural Stem Cells / metabolism*
  • Neurogenesis
  • Oxidation-Reduction


  • Fatty Acids
  • Malonyl Coenzyme A
  • CPT1B protein, mouse
  • Carnitine O-Palmitoyltransferase