School of Life Sciences, Tsinghua-Peking Joint Center for Life Sciences, IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing, 100084, China.
Howard Hughes Medical Institute, Departments of Physiology, Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
Neuron. 2020 Nov 25;108(4):640-650.e4. doi: 10.1016/j.neuron.2020.08.017. Epub 2020 Sep 9.
Animal feeding is controlled by external sensory cues and internal metabolic states. Does it also depend on enteric neurons that sense mechanical cues to signal fullness of the digestive tract? Here, we identify a group of piezo-expressing neurons innervating the Drosophila crop (the fly equivalent of the stomach) that monitor crop volume to avoid food overconsumption. These neurons reside in the pars intercerebralis (PI), a neuro-secretory center in the brain involved in homeostatic control, and express insulin-like peptides with well-established roles in regulating food intake and metabolism. Piezo knockdown in these neurons of wild-type flies phenocopies the food overconsumption phenotype of piezo-null mutant flies. Conversely, expression of either fly Piezo or mammalian Piezo1 in these neurons of piezo-null mutants suppresses the overconsumption phenotype. Importantly, Piezo neurons at the PI are activated directly by crop distension, thus conveying a rapid satiety signal along the "brain-gut axis" to control feeding.
动物的进食受外部感官线索和内部代谢状态的控制。它是否也依赖于能够感知机械线索以发出消化道充盈信号的肠神经元？在这里，我们鉴定了一组表达压电蛋白的神经元，它们支配果蝇的嗉囊（相当于胃的部分），以监测嗉囊容量，避免过度进食。这些神经元位于脑的神经分泌中心——中脑复合体（PI）中，PI 参与体内平衡控制，表达胰岛素样肽，这些肽在调节食物摄入和代谢方面具有重要作用。在野生型果蝇中敲低这些神经元，会表现出与压电突变体果蝇过度进食表型相同的表型。相反，在压电突变体果蝇的这些神经元中表达果蝇 Piezo 或哺乳动物 Piezo1，可抑制过度进食表型。重要的是，PI 中的 Piezo 神经元可被嗉囊扩张直接激活，从而沿着“脑-肠轴”传递快速饱腹感信号，以控制进食。
