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

被引：381

作者：

Knobloch, Marlen ^{[1
,2
]}

Braun, Simon M. G. ^{[1
,2
]}

Zurkirchen, Luis ^{[2
]}

von Schoultz, Carolin ^{[2
]}

Zamboni, Nicola ^{[3
]}

Arauzo-Bravo, Marcos J. ^{[4
]}

Kovacs, Werner J. ^{[2
]}

Karalay, Oezlem ^{[2
]}

Suter, Ueli ^{[2
]}

Machado, Raquel A. C. ^{[1
,2
]}

Roccio, Marta ^{[5
]}

Lutolf, Matthias P. ^{[5
]}

Semenkovich, Clay F. ^{[6
]}

Jessberger, Sebastian ^{[1
,2
]}

机构：

[1] Univ Zurich, Fac Med, Brain Res Inst, CH-8057 Zurich, Switzerland

[2] Swiss Fed Inst Technol, Dept Biol, Inst Mol Hlth Sci, CH-8093 Zurich, Switzerland

[3] Swiss Fed Inst Technol, Dept Biol, Inst Mol Syst Biol, CH-8093 Zurich, Switzerland

[4] Max Planck Inst Mol Biomed, Dept Cell & Dev Biol, D-48149 Munster, Germany

[5] Ecole Polytech Fed Lausanne, Inst Bioengn, CH-1015 Lausanne, Switzerland

[6] Washington Univ, Sch Med, Div Endocrinol Metab & Lipid Res, St Louis, MO 63110 USA

来源：

NATURE | 2013年 / 493卷 / 7431期

基金：

瑞士国家科学基金会;

关键词：

FATTY-ACID SYNTHASE; TRANSGENIC MICE; SPOT; 14; NEUROGENESIS; HOMEOSTASIS; GLUCOSE;

D O I：

10.1038/nature11689

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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(1). 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(2), 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(3-5), that we found to be selectively expressed in low proliferating adult NSPCs. Spot14 reduces the availability of malonyl-CoA(6), 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.

引用

页码：226 / 230

页数：5

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