Mio acts in the Drosophila brain to control nutrient storage and feeding.
Mio acts in the Drosophila brain to control nutrient storage and feeding.
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Mio 在果蝇大脑中发挥作用，控制营养物质的储存和进食。
DOI：
10.1016/j.gene.2015.05.055
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发表时间：
2015
期刊：
影响因子：
3.5
通讯作者：
DiAngelo,JustinR
中科院分区：
文献类型：
--
作者：
Docherty,JamesEB;Manno,JosephE;McDermott,JacquelineE;DiAngelo,JustinR
动物认识到营养素的可用性，并相应地调节这些营养素的摄入和储存。然而，营养传感和随后的行为和代谢变化的分子机制尚未完全理解。Mlx相互作用因子（Mio）是果蝇碳水化合物反应元件结合蛋白（ChREBP）的同源物，在果蝇脂肪体中作为转录因子控制甘油三酯的储存和摄食，提示Mio可能通过营养感应途径协调食物的消耗和代谢。在这里，我们发现Mio在果蝇神经元中的功能是调节摄食和营养储存。泛神经元破坏Miofunction导致增加甘油三酯和糖原储存，这种表型不是由于增加的食物消耗。有趣的是，在胰岛素产生细胞（IPC）中特异性地破坏Mio对营养储存几乎没有影响，但增加了食物消耗，这表明Mio在这些神经元中起作用以控制进食行为。由于Mio是一种转录因子，因此Mio在IPC中控制摄食的一种可能方式是通过调节IPC中产生的神经肽--果蝇胰岛素样肽（dilps）或果蝇磺胺激酶（dsk）的表达。与这一假设相一致，IPC特异性敲低Mioleads增加dilp 3表达，而不影响dilp 2，5 ordsk水平。总之，这项研究表明了Mio在果蝇脑中的新功能，特别是在IPC中，根据营养物质的可用性控制神经肽基因表达，摄食和代谢。
Animals recognize the availability of nutrients and regulate the intake and storage of these nutrients accordingly. However, the molecular mechanisms underlying nutrient sensing and subsequent changes in behavior and metabolism are not fully understood. Mlx interactor (Mio), theDrosophilahomolog of carbohydrate response element binding protein (ChREBP), functions as a transcription factor in the fat body of the fly to control triglyceride storage as well as feeding, suggesting that Mio may act in a nutrient-sensing pathway to coordinate food consumption and metabolism. Here, we show that Mio functions in neurons inDrosophilato regulate feeding and nutrient storage. Pan-neuronal disruption ofMiofunction leads to increased triglyceride and glycogen storage, and this phenotype is not due to increased food consumption. Interestingly, targeted disruption ofMiospecifically in the insulin-producing cells (IPCs) has little effect on nutrient storage, but increases food consumption suggesting that Mio acts in these neurons to control feeding behavior. Since Mio is a transcription factor, one possible way Mio may act in the IPCs to control feeding is through regulating the expression ofDrosophila insulin-like peptides (dilps)ordrosulfakinin(dsk), neuropeptides produced in the IPCs. Consistent with this hypothesis, IPC-specific knockdown ofMioleads to an increase indilp3expression, while not affectingdilp2,5ordsklevels. Together, this study indicates a new function for Mio in theDrosophilabrain and specifically in the IPCs, controlling neuropeptide gene expression, feeding and metabolism in accordance with nutrient availability.