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

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Knobloch Marlen, Pilz Gregor-Alexander, Ghesquière Bart, Kovacs Werner J, Wegleiter Thomas, Moore Darcie L, Hruzova Martina, Zamboni Nicola, Carmeliet Peter, Jessberger Sebastian,
Project Elucidating the Role of Lipid Metabolism for Life-long Neurogenesis in the Mammalian Brain
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Original article (peer-reviewed)

Journal Cell reports
Page(s) 2144 - 2155
Title of proceedings Cell reports
DOI 10.1016/j.celrep.2017.08.029

Open Access

URL https://serval.unil.ch/resource/serval:BIB_09A7951D55FF.P001/REF.pdf
Type of Open Access Publisher (Gold Open Access)

Abstract

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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