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

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.