Steroid signaling mediates nutritional regulation of juvenile body growth via IGF-binding protein in Drosophila
Steroid signaling mediates nutritional regulation of juvenile body growth via IGF-binding protein in Drosophila
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DOI：
10.1073/pnas.1718834115
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发表时间：
2018-06-05
影响因子：
11.1
通讯作者：
Hyun, Seogang
中科院分区：
文献类型：
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作者：
Lee, Gang Jun;Han, Gangsik;Hyun, Seogang
幼年生长期的营养状况很大程度上影响成年后的体型。众所周知，胰岛素/胰岛素样生长因子信号传导 (IIS)/雷帕霉素靶点 (TOR) 营养感应途径可根据营养条件调节生长和代谢。然而，关于内分泌途径如何将营养信息传递给不同代谢器官以调节有机体生长的信息有限。在这里，我们证明了成虫形态发生蛋白-Late 2 (Imp-L2)，胰岛素样生长因子结合蛋白 7 (IGFBP7) 的果蝇同源物，在生物体生长的营养控制中发挥着关键作用。幼虫生长期间的营养限制会导致成虫体型过小，而 Imp-L2 突变可大大减少这种情况。我们描绘了一条途径，其中营养限制会增加类固醇激素蜕皮激素的水平，进而触发脂肪体（果蝇脂肪器官）产生蜕皮激素信号依赖性Imp-L2，从而减弱外周IIS和身体生长。令人惊讶的是，这种内分泌途径的运作独立于脂肪体 TOR 内部营养传感器，长期以来，该传感器被认为是营养依赖性生长的控制中心。我们的研究揭示了一种以前未被认识的内分泌回路，介导营养依赖性青少年生长，这也可能与青春期经常观察到的胰岛素抵抗有关。
Nutritional condition during the juvenile growth period considerably affects final adult size. The insulin/insulin-like growth factor signaling (IIS)/target of rapamycin (TOR) nutrient-sensing pathway is known to regulate growth and metabolism in response to nutritional conditions. However, there is limited information on how endocrine pathways communicate nutritional information to different metabolic organs to regulate organismal growth. Here, we show that Imaginal morphogenesis protein-Late 2 (Imp-L2), a Drosophila homolog of insulin-like growth factor-binding protein 7 (IGFBP7), plays a key role in the nutritional control of organismal growth. Nutritional restriction during the larval growth period causes undersized adults, which is largely diminished by Imp-L2 mutation. We delineate a pathway in which nutritional restriction increases levels of the steroid hormone ecdysone, which, in turn, triggers ecdysone signaling-dependent Imp-L2 production from the fat body, a fly adipose organ, thereby attenuating peripheral IIS and body growth. Surprisingly, this endocrine pathway operates independent of the fat-body-TOR internal nutrient sensor, long believed to be the control center for nutrition-dependent growth. Our study reveals a previously unrecognized endocrine circuit mediating nutrition-dependent juvenile growth, which could also potentially be related to the insulin resistance frequently observed in puberty.