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

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

Author information

1
Laboratory of Neural Plasticity, Faculty of Medicine and Science, Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland. Electronic address: marlen.knobloch@unil.ch.
2
Laboratory of Neural Plasticity, Faculty of Medicine and Science, Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland.
3
VIB Metabolomics Expertise Center, 3000 Leuven, Belgium; Laboratory of Angiogenesis & Vascular Metabolism, Vesalius Research Center VIB, 3000 Leuven, Belgium.
4
Institute of Molecular Health Sciences, Department of Biology, ETH Zurich, 8093 Zurich, Switzerland.
5
Institute of Molecular Systems Biology, Department of Biology, ETH Zurich, 8093 Zurich, Switzerland.
6
Laboratory of Angiogenesis & Vascular Metabolism, Vesalius Research Center VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis & Vascular Metabolism, Department of Oncology, KU Leuven, 3000 Leuven, Belgium.
7
Laboratory of Neural Plasticity, Faculty of Medicine and Science, Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland. Electronic address: jessberger@hifo.uzh.ch.

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.

KEYWORDS:

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

PMID:
28854364
PMCID:
PMC5583518
DOI:
10.1016/j.celrep.2017.08.029
[Indexed for MEDLINE]
Free PMC Article

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