Hyun Moonjung, Davis Kristen, Lee Inhwan, Kim Jeongho, Dumur Catherine, You Young-Jai
Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia, USA.
Department of Biological Sciences, Inha University, Incheon, 402-751, South Korea.
Sci Rep. 2016 Apr 21;6:24841. doi: 10.1038/srep24841.
Animals change feeding behavior depending on their metabolic status; starved animals are eager to eat and satiated animals stop eating. C. elegans exhibits satiety quiescence under certain conditions that mimics many aspects of post-prandial sleep in mammals. Here we show that this feeding behavior depends on fat metabolism mediated by the SREBP-SCD pathway, an acetyl-CoA carboxylase (ACC) and certain nuclear hormone receptors (NRs). Mutations of the genes in the SREBP-SCD pathway reduce satiety quiescence. An RNA interference (RNAi) screen of the genes that regulate glucose and fatty acid metabolism identified an ACC necessary for satiety quiescence in C. elegans. ACC catalyzes the first step in de novo fatty acid biosynthesis known to be downstream of the SREBP pathway in mammals. We identified 28 NRs by microarray whose expression changes during refeeding after being starved. When individually knocked down by RNAi, 11 NRs among 28 affect both fat storage and satiety behavior. Our results show that the major fat metabolism pathway regulates feeding behavior and NRs could be the mediators to link the feeding behavior to the metabolic changes.
动物会根据其代谢状态改变摄食行为；饥饿的动物急于进食，而饱腹的动物则停止进食。秀丽隐杆线虫在某些条件下会表现出饱腹感静止，这类似于哺乳动物餐后睡眠的许多方面。在这里，我们表明这种摄食行为取决于由SREBP-SCD途径介导的脂肪代谢，该途径涉及乙酰辅酶A羧化酶（ACC）和某些核激素受体（NRs）。SREBP-SCD途径中的基因突变会减少饱腹感静止。对调节葡萄糖和脂肪酸代谢的基因进行RNA干扰（RNAi）筛选，确定了秀丽隐杆线虫饱腹感静止所必需的一种ACC。ACC催化从头合成脂肪酸的第一步，这在哺乳动物中已知是SREBP途径的下游反应。我们通过微阵列鉴定出28种NRs，其表达在饥饿后重新进食期间发生变化。当通过RNAi单独敲低时，28种NRs中的11种会影响脂肪储存和饱腹感行为。我们的结果表明，主要的脂肪代谢途径调节摄食行为，而NRs可能是将摄食行为与代谢变化联系起来的介质。
