A nutrient-responsive hormonal circuit mediates an inter-tissue program regulating metabolic homeostasis in adult Drosophila.
A nutrient-responsive hormonal circuit mediates an inter-tissue program regulating metabolic homeostasis in adult Drosophila.
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DOI：
10.1038/s41467-021-25445-2
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发表时间：
2021-08-30
影响因子：
16.6
通讯作者：
Halberg KV
中科院分区：
文献类型：
--
作者：
Koyama T;Terhzaz S;Naseem MT;Nagy S;Rewitz K;Dow JAT;Davies SA;Halberg KV
动物通过调节专门器官的活动来维持代谢稳态，这些器官调节内部代谢以适应外部条件。然而，协调这些功能的激素信号的特征并不完全。在这里，我们表明，在果蝇中枢神经系统的6个神经分泌细胞通过释放卡帕激素，哺乳动物神经介肽U的同系物，激活卡帕受体（CapaR）在外周组织控制能量稳态循环营养水平。Capa/CapaR信号传导的丧失导致肠道运动功能减退和营养吸收受损，这逐渐耗尽内部营养储存并缩短生物体寿命。相反，增加Capa/CapaR活性增加液体和废物排泄。此外，Capa/CapaR抑制胰高血糖素样脂肪动力激素从心体的释放，这限制了脂肪组织的能量动员，以避免有害的高血糖症。我们的研究结果表明，Capa/CapaR电路占据了一个中心节点的稳态程序，促进消化和吸收的营养物质，并调节全身能量平衡。在进食和禁食状态下维持代谢稳态对动物的生存至关重要。在这里，作者表明，卡帕激素信号，同源哺乳动物神经介肽U，有助于控制稳态通过调节营养吸收和能量储存在果蝇。
Animals maintain metabolic homeostasis by modulating the activity of specialized organs that adjust internal metabolism to external conditions. However, the hormonal signals coordinating these functions are incompletely characterized. Here we show that six neurosecretory cells in the Drosophila central nervous system respond to circulating nutrient levels by releasing Capa hormones, homologs of mammalian neuromedin U, which activate the Capa receptor (CapaR) in peripheral tissues to control energy homeostasis. Loss of Capa/CapaR signaling causes intestinal hypomotility and impaired nutrient absorption, which gradually deplete internal nutrient stores and reduce organismal lifespan. Conversely, increased Capa/CapaR activity increases fluid and waste excretion. Furthermore, Capa/CapaR inhibits the release of glucagon-like adipokinetic hormone from the corpora cardiaca, which restricts energy mobilization from adipose tissue to avoid harmful hyperglycemia. Our results suggest that the Capa/CapaR circuit occupies a central node in a homeostatic program that facilitates the digestion and absorption of nutrients and regulates systemic energy balance. Maintaining metabolic homeostasis during feeding and fasting states is critical to animal survival. Here the authors show that Capa hormone signaling, homologs to mammalian Neuromedin U, helps control homeostasis via regulation of nutrient uptake and energy storage in Drosophila.
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影响因子：
64.5
作者：
Dietrich MO;Zimmer MR;Bober J;Horvath TL
通讯作者：
Horvath TL
影响因子：
6.7
作者：
Benguettat O;Jneid R;Soltys J;Loudhaief R;Brun-Barale A;Osman D;Gallet A
通讯作者：
Gallet A
DOI：
10.1152/ajpregu.00584.2001
发表时间：
2002-05-01
影响因子：
2.8
作者：
Kean, L;Cazenave, W;Dow, JAT
通讯作者：
Dow, JAT
影响因子：
8.8
作者：
Dutta, Devanjali;Dobson, Adam J.;Buchon, Nicolas
通讯作者：
Buchon, Nicolas
影响因子：
4.8
作者：
Ivanov, TR;Lawrence, CB;Luckman, SM
通讯作者：
Luckman, SM