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.
authors.affiliation: Brain Research Institute, Faculty of Medicine, University of Zurich, 8057 Zurich, Switzerland.
authors.forename: Marlen
authors.initials: M
authors.lastname: Knobloch
authors.forename: Simon M G
authors.initials: SM
authors.lastname: Braun
authors.forename: Luis
authors.initials: L
authors.lastname: Zurkirchen
authors.forename: Carolin
authors.initials: C
authors.lastname: von Schoultz
authors.forename: Nicola
authors.initials: N
authors.lastname: Zamboni
authors.forename: Marcos J
authors.initials: MJ
authors.lastname: Araúzo-Bravo
authors.forename: Werner J
authors.initials: WJ
authors.lastname: Kovacs
authors.forename: Ozlem
authors.initials: O
authors.lastname: Karalay
authors.forename: Ueli
authors.initials: U
authors.lastname: Suter
authors.forename: Raquel A C
authors.initials: RA
authors.lastname: Machado
authors.forename: Marta
authors.initials: M
authors.lastname: Roccio
authors.forename: Matthias P
authors.initials: MP
authors.lastname: Lutolf
authors.forename: Clay F
authors.initials: CF
authors.lastname: Semenkovich
authors.forename: Sebastian
authors.initials: S
authors.lastname: Jessberger
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D049109:Cell Proliferation; D018891:Dentate Gyrus / Q000378:metabolism; D064429:Fatty Acid Synthases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D050155:Lipogenesis; D008316:Malonyl Coenzyme A / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; C501477:Thrsp protein, mouse; D014157:Transcription Factors; D008316:Malonyl Coenzyme A; D064429:Fatty Acid Synthases