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蛋白质对所有生物体都是必不可少的；然而，过量摄入蛋白质会产生不良影响，如高氨血症。尽管对蛋白质缺乏的反应机制已经得到了很好的研究，但我们对生物体如何自适应地抑制过量蛋白质摄入的理解仍存在重大差距。在本研究中，我们利用果蝇黑腹果蝇发现，肠内分泌细胞在高蛋白饮食（HPD）下分泌的肽激素CCHaide1（CCHa1）对抑制蛋白质的过度消耗至关重要。肠道来源的CCHa1被一小部分肠神经元接收，这些神经元产生短神经肽F，从而调节蛋白质特异性饱腹感 标签: 蛋白质、果蝇进食、肠道激素 |
A high-protein diet-responsive gut hormone regulates behavioral and metabolic optimization in Drosophila melanogaster
Yuto Yoshinari, Takashi Nishimura, Taishi Yoshii, Shu Kondo, Hiromu Tanimoto, Tomoe Kobayashi, Makoto Matsuyama & Ryusuke Niwa
Nature Communications volume 15, Article number: 10819 (2024)
Abstract
Protein is essential for all living organisms; however, excessive protein intake can have adverse effects, such as hyperammonemia. Although mechanisms responding to protein deficiency are well-studied, there is a significant gap in our understanding of how organisms adaptively suppress excessive protein intake. In the present study, utilizing the fruit fly, Drosophila melanogaster, we discover that the peptide hormone CCHamide1 (CCHa1), secreted by enteroendocrine cells in response to a high-protein diet (HPD), is vital for suppressing overconsumption of protein. Gut-derived CCHa1 is received by a small subset of enteric neurons that produce short neuropeptide F, thereby modulating protein-specific satiety. Importantly, impairment of the CCHa1-mediated gut-enteric neuronal axis results in ammonia accumulation and a shortened lifespan under HPD conditions. Collectively, our findings unravel the crosstalk of gut hormone and neuronal pathways that orchestrate physiological responses to prevent and adapt to dietary protein overload.
蛋白质对所有生物体都是必不可少的；然而，过量摄入蛋白质会产生不良影响，如高氨血症。尽管对蛋白质缺乏的反应机制已经得到了很好的研究，但我们对生物体如何自适应地抑制过量蛋白质摄入的理解仍存在重大差距。在本研究中，我们利用果蝇黑腹果蝇发现，肠内分泌细胞在高蛋白饮食（HPD）下分泌的肽激素CCHaide1（CCHa1）对抑制蛋白质的过度消耗至关重要。肠道来源的CCHa1被一小部分肠神经元接收，这些神经元产生短神经肽F，从而调节蛋白质特异性饱腹感。重要的是，在HPD条件下，CCHa1介导的肠道-肠神经元轴的损伤导致氨积累和寿命缩短。总的来说，我们的发现揭示了肠道激素和神经元通路的相互作用，这些通路协调生理反应以预防和适应饮食中的蛋白质超载。
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a The gut and capillary feeding (CAFÉ) assay showing the experimental scheme. b Screening of enteroendocrine hormones, which affect feeding amount in the CAFÉ assay. c The CAFÉ assay with CCHa1 RNAi in the Gut EECs (prosts), EECs of R5 region midgut (AstA), and brain (nSybbrain). d Immunostaining images of the midgut from control or gut-specific CCHa1 RNAi flies. CCHa1 (Red), Prospero (white), and DAPI (blue) are shown. In the bottom images, white broken lines show the outlines of the midgut. Scale bar, 50 µm. e Two-choice feeding experiment with CAFÉ assay. Consumption of sucrose (left), yeast autolysate (centre), and preference (right) of control or gut-specific CCHa1 RNAi flies is shown. In this and the following two-choice CAFÉ assay figures, each dot presents a sample of eight flies. In the preference graph, S means sucrose, Y means yeast autolysate. f Two-choice feeding experiment with CAFÉ assay. Consumption of sucrose (left), tryptone (centre), and preference (right) is shown. g Number of sips of sucrose (left) and yeast autolysate (right) of CCHa1 RNAi or control flies measured using the flyPAD system. In this and the following flyPAD assay figures, a dot presents the number of sips by a single fly from each food source measured separately. Numbers of samples assessed (n) are shown in the graphs. For all bar graphs, means and SEMs with all data points are shown. For box plots with dots, the median, 25th and 75th percentile lines are shown. Whiskers extend 1.5 times the interquartile range from the 25th and 75th percentiles. Statistics: One-way ANOVA followed by Dunnett’s test (b), two-tailed Student’s t test (c, e, f), two-sided Wilcoxon rank sum test (g). p values are shown in the graphs.
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©2012-2025 图拉扬科技 版权所有,并保留所有权利,未经授权 不得复制或建立镜像. 蜀ICP备2021003222号-1
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20181112000193
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