Metabolic control of adult neural stem cell activity by Fasn-dependent lipogenesis

Marlen Knobloch; Simon M.G. Braun; Luis Zurkirchen; Carolin Von Schoultz; Nicola Zamboni; Marcos J. Araúzo-Bravo; Werner J. Kovacs; Özlem Karalay; Ueli Suter; Raquel A.C. MacHado; Marta Roccio; Matthias P. Lutolf; Clay F. Semenkovich; Sebastian Jessberger

doi:10.1038/nature11689

Metabolic control of adult neural stem cell activity by Fasn-dependent lipogenesis

Marlen Knobloch, Simon M.G. Braun, Luis Zurkirchen, Carolin Von Schoultz, Nicola Zamboni, Marcos J. Araúzo-Bravo, Werner J. Kovacs, Özlem Karalay, Ueli Suter, Raquel A.C. MacHado, Marta Roccio, Matthias P. Lutolf, Clay F. Semenkovich, Sebastian Jessberger

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Abstract

Mechanisms controlling the proliferative activity of neural stem and progenitor cells (NSPCs) have a pivotal role to ensure life-long neurogenesis in the mammalian brain. How metabolic programs are coupled with NSPC activity remains unknown. Here we show that fatty acid synthase (Fasn), the key enzyme of de novo lipogenesis, is highly active in adult NSPCs and that conditional deletion of Fasn in mouse NSPCs impairs adult neurogenesis. The rate of de novo lipid synthesis and subsequent proliferation of NSPCs is regulated by Spot14, a gene previously implicated in lipid metabolism, that we found to be selectively expressed in low proliferating adult NSPCs. Spot14 reduces the availability of malonyl-CoA, which is an essential substrate for Fasn to fuel lipogenesis. Thus, we identify here a functional coupling between the regulation of lipid metabolism and adult NSPC proliferation.

Original language	English
Pages (from-to)	226-230
Number of pages	5
Journal	Nature
Volume	493
Issue number	7431
DOIs	https://doi.org/10.1038/nature11689
State	Published - Jan 10 2013

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Knobloch, M., Braun, S. M. G., Zurkirchen, L., Von Schoultz, C., Zamboni, N., Araúzo-Bravo, M. J., Kovacs, W. J., Karalay, Ö., Suter, U., MacHado, R. A. C., Roccio, M., Lutolf, M. P., Semenkovich, C. F., & Jessberger, S. (2013). Metabolic control of adult neural stem cell activity by Fasn-dependent lipogenesis. Nature, 493(7431), 226-230. https://doi.org/10.1038/nature11689

@article{5a103c51d9004f9ead6a5b2eb962ca1c,

title = "Metabolic control of adult neural stem cell activity by Fasn-dependent lipogenesis",

abstract = "Mechanisms controlling the proliferative activity of neural stem and progenitor cells (NSPCs) have a pivotal role to ensure life-long neurogenesis in the mammalian brain. How metabolic programs are coupled with NSPC activity remains unknown. Here we show that fatty acid synthase (Fasn), the key enzyme of de novo lipogenesis, is highly active in adult NSPCs and that conditional deletion of Fasn in mouse NSPCs impairs adult neurogenesis. The rate of de novo lipid synthesis and subsequent proliferation of NSPCs is regulated by Spot14, a gene previously implicated in lipid metabolism, that we found to be selectively expressed in low proliferating adult NSPCs. Spot14 reduces the availability of malonyl-CoA, which is an essential substrate for Fasn to fuel lipogenesis. Thus, we identify here a functional coupling between the regulation of lipid metabolism and adult NSPC proliferation.",

author = "Marlen Knobloch and Braun, {Simon M.G.} and Luis Zurkirchen and {Von Schoultz}, Carolin and Nicola Zamboni and Ara{\'u}zo-Bravo, {Marcos J.} and Kovacs, {Werner J.} and {\"O}zlem Karalay and Ueli Suter and MacHado, {Raquel A.C.} and Marta Roccio and Lutolf, {Matthias P.} and Semenkovich, {Clay F.} and Sebastian Jessberger",

note = "Funding Information: Acknowledgements We thank S. Aigner, D. C. Lie, F. H. Gage and members of the Jessberger group for conceptual input; S. Kobel, C. Fischer, K. Walter, P. Sidiropoulos, T. Buch, B. Becher, P. Pelczar, P. L{\"o}tscher, A. J. Eisch and D. C. Lagace for experimental help or reagents; and the Light Microscopy and Screening Center (LMSC) of the ETH Zurich and the BioImaging and Optics Platform (BIOP) of the EPFL for help with imaging. This study was supported by the NCCR Neural Plasticity and Repair, Swiss National Science Foundation, TH grant (ETH-01 08-1), Zurich Neuroscience Center (ZNZ), Novartis Foundation, Theodore Ott Foundation, and the EMBO Young Investigator program (to S.J.). M.K. was supported by the Janggen-P{\"o}hn foundation.",

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doi = "10.1038/nature11689",

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T1 - Metabolic control of adult neural stem cell activity by Fasn-dependent lipogenesis

AU - Knobloch, Marlen

AU - Braun, Simon M.G.

AU - Zurkirchen, Luis

AU - Von Schoultz, Carolin

AU - Zamboni, Nicola

AU - Araúzo-Bravo, Marcos J.

AU - Kovacs, Werner J.

AU - Karalay, Özlem

AU - Suter, Ueli

AU - MacHado, Raquel A.C.

AU - Roccio, Marta

AU - Lutolf, Matthias P.

AU - Semenkovich, Clay F.

AU - Jessberger, Sebastian

N1 - Funding Information: Acknowledgements We thank S. Aigner, D. C. Lie, F. H. Gage and members of the Jessberger group for conceptual input; S. Kobel, C. Fischer, K. Walter, P. Sidiropoulos, T. Buch, B. Becher, P. Pelczar, P. Lötscher, A. J. Eisch and D. C. Lagace for experimental help or reagents; and the Light Microscopy and Screening Center (LMSC) of the ETH Zurich and the BioImaging and Optics Platform (BIOP) of the EPFL for help with imaging. This study was supported by the NCCR Neural Plasticity and Repair, Swiss National Science Foundation, TH grant (ETH-01 08-1), Zurich Neuroscience Center (ZNZ), Novartis Foundation, Theodore Ott Foundation, and the EMBO Young Investigator program (to S.J.). M.K. was supported by the Janggen-Pöhn foundation.

PY - 2013/1/10

Y1 - 2013/1/10

N2 - Mechanisms controlling the proliferative activity of neural stem and progenitor cells (NSPCs) have a pivotal role to ensure life-long neurogenesis in the mammalian brain. How metabolic programs are coupled with NSPC activity remains unknown. Here we show that fatty acid synthase (Fasn), the key enzyme of de novo lipogenesis, is highly active in adult NSPCs and that conditional deletion of Fasn in mouse NSPCs impairs adult neurogenesis. The rate of de novo lipid synthesis and subsequent proliferation of NSPCs is regulated by Spot14, a gene previously implicated in lipid metabolism, that we found to be selectively expressed in low proliferating adult NSPCs. Spot14 reduces the availability of malonyl-CoA, which is an essential substrate for Fasn to fuel lipogenesis. Thus, we identify here a functional coupling between the regulation of lipid metabolism and adult NSPC proliferation.

AB - Mechanisms controlling the proliferative activity of neural stem and progenitor cells (NSPCs) have a pivotal role to ensure life-long neurogenesis in the mammalian brain. How metabolic programs are coupled with NSPC activity remains unknown. Here we show that fatty acid synthase (Fasn), the key enzyme of de novo lipogenesis, is highly active in adult NSPCs and that conditional deletion of Fasn in mouse NSPCs impairs adult neurogenesis. The rate of de novo lipid synthesis and subsequent proliferation of NSPCs is regulated by Spot14, a gene previously implicated in lipid metabolism, that we found to be selectively expressed in low proliferating adult NSPCs. Spot14 reduces the availability of malonyl-CoA, which is an essential substrate for Fasn to fuel lipogenesis. Thus, we identify here a functional coupling between the regulation of lipid metabolism and adult NSPC proliferation.

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U2 - 10.1038/nature11689

DO - 10.1038/nature11689

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AN - SCOPUS:84872169944

SN - 0028-0836

VL - 493

SP - 226

EP - 230

JO - Nature

JF - Nature

IS - 7431

ER -

Metabolic control of adult neural stem cell activity by Fasn-dependent lipogenesis

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