Section for Cell and Neurobiology, Department of Biology, University of Copenhagen, Universitetsparken 15, Copenhagen, Denmark.
Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Nat Commun. 2021 Aug 30;12(1):5178. doi: 10.1038/s41467-021-25445-2.
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.
动物通过调节专门器官的活性来维持代谢稳态，从而使内部代谢适应外部条件。然而，协调这些功能的激素信号还没有完全被描述。在这里，我们发现果蝇中枢神经系统中的 6 种神经分泌细胞通过释放 Capa 激素对循环营养水平做出反应，Capa 激素是哺乳动物神经肽 U 的同源物，它可以激活外周组织中的 Capa 受体 (CapaR) 来控制能量稳态。Capa/CapaR 信号的缺失会导致肠道蠕动减弱和营养吸收受损，这会逐渐耗尽体内营养储存并缩短生物体寿命。相反，增加 Capa/CapaR 活性会增加液体和废物的排泄。此外，Capa/CapaR 抑制了来自心侧体的胰高血糖素样脂肪激活激素的释放，这限制了脂肪组织中能量的动员，以避免有害的高血糖。我们的研究结果表明，Capa/CapaR 回路占据了一个有助于消化和吸收营养物质以及调节全身能量平衡的稳态程序的中心节点。
