A 13C isotope labeling strategy reveals the influence of insulin signaling on lipogenesis in C-elegans
A 13C isotope labeling strategy reveals the influence of insulin signaling on lipogenesis in C-elegans
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DOI：
10.1016/j.cmet.2008.08.007
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发表时间：
2008-09-03
期刊：
影响因子：
29
通讯作者：
Van Gilst, Marc R.
中科院分区：
文献类型：
--
作者：
Perez, Carissa L.;Van Gilst, Marc R.
虽然对秀丽隐杆线虫的研究已经确定了许多与脂肪储存有关的基因，但下一步是确定这些因素如何影响体内脂质代谢。我们开发了一种C-13同位素测定方法，以量化秀丽隐杆线虫膳食脂肪吸收和重新合成对脂肪储存和膜脂生成的贡献，确定蠕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的几个长期突变导致甘油三酯和磷脂中合成脂肪的水平显著升高。这种脂肪合成的升高完全依赖于daf-16/FoxO。然而，daf-2的其他长寿命等位基因并没有增加脂肪合成，这表明胰岛素受体的位点特异性突变可以不同程度地影响寿命和代谢，并且daf-2突变体的寿命并不需要提高脂质合成。
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 C-13 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.