Multi-omics Analyses of Starvation Responses Reveal a Central Role for Lipoprotein Metabolism in Acute Starvation Survival in C. elegans
Multi-omics Analyses of Starvation Responses Reveal a Central Role for Lipoprotein Metabolism in Acute Starvation Survival in C. elegans
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DOI：
10.1016/j.cels.2017.06.004
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发表时间：
2017-07-26
期刊：
影响因子：
9.3
通讯作者：
Frgeman, Nils J.
中科院分区：
文献类型：
--
作者：
Harvald, Eva Bang;Sprenger, Richard R.;Frgeman, Nils J.
饥饿会引起全面的代谢变化，目前尚未完全了解。在这里，我们使用定量蛋白质组学和 RNA 测序来检查野生型秀丽隐杆线虫和缺乏转录因子 HLH-30 的动物的暂时饥饿反应。我们的研究结果表明，饥饿会暂时改变数百种蛋白质和 mRNA 的丰度，其中许多蛋白质和 mRNA 参与中央代谢途径，包括脂蛋白代谢。我们证明，敲低编码两种不同脂蛋白的 vit-1 或 vit-5 可以防止 hlh-30 动物在饥饿下过早死亡。我们进一步表明，hlh-30 动物在饥饿下肠道脂滴的大小和数量发生了改变，这可以通过敲低 vit-1 来挽救。综上所述，这表明 hlh-30 动物在饥饿下的存活与肠道脂质储存的调节密切相关。我们提供迄今为止最详细的饥饿反应多组学分析，作为进一步饥饿机制研究的资源。
Starvationcauses comprehensivemetabolicchanges, which are still not fully understood. Here, we used quantitative proteomics and RNA sequencing to examine the temporal starvation responses in wildtype Caenorhabditis elegans and animals lacking the transcription factor HLH-30. Our findings show that starvation alters the abundance of hundreds of proteins and mRNAs in a temporal manner, many of which are involved in central metabolic pathways, including lipoprotein metabolism. We demonstrate that premature death of hlh-30 animals under starvation can be prevented by knockdown of either vit-1 or vit-5, encoding two different lipoproteins. We further showthat the size and number of intestinal lipid droplets under starvation are altered in hlh-30 animals, which can be rescued by knockdown of vit-1. Taken together, this indicates that survival of hlh-30 animals under starvation is closely linked to regulation of intestinal lipid stores. We provide the most detailed poly-omic analysis of starvation responses to date, which serves as a resource for further mechanistic studies of starvation.