Document Detail


Metabolic control of adult neural stem cell activity by Fasn-dependent lipogenesis.
MedLine Citation:
PMID:  23201681     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Marlen Knobloch; Simon M G Braun; Luis Zurkirchen; Carolin von Schoultz; Nicola Zamboni; Marcos J Araúzo-Bravo; Werner J Kovacs; Ozlem Karalay; Ueli Suter; Raquel A C Machado; Marta Roccio; Matthias P Lutolf; Clay F Semenkovich; Sebastian Jessberger
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-12-02
Journal Detail:
Title:  Nature     Volume:  493     ISSN:  1476-4687     ISO Abbreviation:  Nature     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-10     Completed Date:  2013-02-26     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  England    
Other Details:
Languages:  eng     Pagination:  226-30     Citation Subset:  IM    
Data Bank Information
Bank Name/Acc. No.:
GEO/GSE27391
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MeSH Terms
Descriptor/Qualifier:
Adult Stem Cells / cytology,  metabolism*
Animals
Cell Proliferation
Dentate Gyrus / metabolism
Fatty Acid Synthases / deficiency,  genetics,  metabolism*
Gene Expression Profiling
Hippocampus / cytology,  metabolism
Lipogenesis*
Malonyl Coenzyme A / metabolism
Mice
Mice, Transgenic
Neural Stem Cells / cytology,  metabolism*
Neurogenesis
Nuclear Proteins / genetics,  metabolism
Transcription Factors / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
P30 DK020579/DK/NIDDK NIH HHS; R01 DK076729/DK/NIDDK NIH HHS; R01 DK088083/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Nuclear Proteins; 0/Thrsp protein, mouse; 0/Transcription Factors; 524-14-1/Malonyl Coenzyme A; EC 2.3.1.85/Fatty Acid Synthases
Comments/Corrections
Comment In:
Cell Metab. 2013 Feb 5;17(2):153-5   [PMID:  23395162 ]

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