Perez Carissa L, Van Gilst Marc R
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Cell Metab. 2008 Sep;8(3):266-74. doi: 10.1016/j.cmet.2008.08.007.
Although studies in C. elegans have identified numerous genes involved in fat storage, the next step is to determine how these factors actually affect in vivo lipid metabolism. We have developed a (13)C isotope assay to quantify the contribution of dietary fat absorption and de novo synthesis to fat storage and membrane lipid production in C. elegans, establishing the means by which worms obtain and process fatty acids. We applied this method to characterize how insulin signaling affects lipid physiology. Several long-lived mutations in the insulin receptor gene daf-2 resulted in significantly higher levels of synthesized fats in triglycerides and phospholipids. This elevation of fat synthesis was completely dependent upon daf-16/FoxO. Other long-lived alleles of daf-2 did not increase fat synthesis, however, suggesting that site-specific mutations in the insulin receptor can differentially influence longevity and metabolism, and that elevated lipid synthesis is not required for the longevity of daf-2 mutants.
尽管对秀丽隐杆线虫的研究已经鉴定出许多参与脂肪储存的基因,但下一步是确定这些因素实际上如何影响体内脂质代谢。我们开发了一种碳-13同位素测定法,以量化饮食脂肪吸收和从头合成对秀丽隐杆线虫脂肪储存和膜脂生成的贡献,从而确定线虫获取和加工脂肪酸的方式。我们应用这种方法来表征胰岛素信号如何影响脂质生理。胰岛素受体基因daf-2中的几个长寿突变导致甘油三酯和磷脂中合成脂肪的水平显著升高。脂肪合成的这种升高完全依赖于daf-16/FoxO。然而,daf-2的其他长寿等位基因并没有增加脂肪合成,这表明胰岛素受体中的位点特异性突变可以不同地影响寿命和代谢,并且daf-2突变体的长寿并不需要脂质合成升高。