Functional Pharmacology, Department of Neuroscience, Uppsala University, 751 24 Uppsala, Sweden;
Functional Pharmacology, Department of Neuroscience, Uppsala University, 751 24 Uppsala, Sweden.
Proc Natl Acad Sci U S A. 2020 Mar 31;117(13):7401-7408. doi: 10.1073/pnas.1914037117. Epub 2020 Mar 16.
The intake of macronutrients is crucial for the fitness of any animal and is mainly regulated by peripheral signals to the brain. How the brain receives and translates these peripheral signals or how these interactions lead to changes in feeding behavior is not well-understood. We discovered that 2 crustacean cardioactive peptide (CCAP)-expressing neurons in adults regulate feeding behavior and metabolism. Notably, loss of CCAP, or knocking down the CCAP receptor (CCAP-R) in 2 dorsal median neurons, inhibits the release of neuropeptide F (NPF), which regulates feeding behavior. Furthermore, under starvation conditions, flies normally have an increased sensitivity to sugar; however, loss of CCAP, or CCAP-R in 2 dorsal median NPF neurons, inhibited sugar sensitivity in satiated and starved flies. Separate from its regulation of NPF signaling, the CCAP peptide also regulates triglyceride levels. Additionally, genetic and optogenetic studies demonstrate that CCAP signaling is necessary and sufficient to stimulate a reflexive feeding behavior, the proboscis extension reflex (PER), elicited when external food cues are interpreted as palatable. Dopaminergic signaling was also sufficient to induce a PER. On the other hand, although necessary, NPF neurons were not able to induce a PER. These data illustrate that the CCAP peptide is a central regulator of feeding behavior and metabolism in adult flies, and that NPF neurons have an important regulatory role within this system.
宏量营养素的摄入对任何动物的健康都至关重要，主要通过外周信号来调节大脑。大脑如何接收和翻译这些外周信号，或者这些相互作用如何导致摄食行为的变化，目前还不是很清楚。我们发现，成年果蝇中 2 个甲壳动物心脏活性肽（CCAP）表达神经元调节摄食行为和代谢。值得注意的是，CCAP 的缺失，或敲降 2 个背侧中脑神经元中的 CCAP 受体（CCAP-R），会抑制调节摄食行为的神经肽 F（NPF）的释放。此外，在饥饿条件下，果蝇通常对糖的敏感性增加；然而，CCAP 的缺失，或 2 个背侧中脑神经元中的 CCAP-R 和 NPF 神经元的缺失，会抑制饱食和饥饿果蝇对糖的敏感性。除了对 NPF 信号的调节作用外，CCAP 肽还调节甘油三酯水平。此外，遗传和光遗传学研究表明，CCAP 信号对于刺激反射性摄食行为（伸喙反射，PER）是必需和充分的，当外部食物线索被解释为美味时，就会引发 PER。多巴胺能信号也足以诱导 PER。另一方面，尽管是必需的，但 NPF 神经元不能诱导 PER。这些数据表明，CCAP 肽是成年果蝇摄食行为和代谢的中枢调节剂，而 NPF 神经元在这个系统中具有重要的调节作用。
