Liu Yating, Li Qian, Tian Guojing, Zhou Xinyi, Chen Panpan, Chen Bo, Shan Zhao, Qi Bin
Southwest United Graduate School, Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory of Conservation and Utilization of Bio-resources in Yunnan Center for Life Sciences, School of Life Sciences, Yunnan University, Kunming, China.
Nat Commun. 2024 Dec 4;15(1):10582. doi: 10.1038/s41467-024-55013-3.
All organisms depend on food digestion for survival, yet the brain-gut signaling mechanisms that regulate this process are not fully understood. Here, using an established C. elegans digestion model, we uncover a pathway in which neuronal ROS (free radicals) signal the intestine to suppress digestion. Genetic screening reveals that reducing genes responsible for maintaining ROS balance increases free radicals and decreases digestion. PRDX-2 knockout in olfactory neurons (AWC) elevates ROS and reduces digestive capacity, mediated by the neuropeptide NLP-1 and activation of the mitochondrial unfolded protein response (UPR) in the intestine. Additionally, over-expressing nlp-1 or ablating AWC neurons both trigger UPR and inhibit digestion. These findings reveal a brain-gut connection in which neuronal PRDX-2-mediated ROS signaling modulates food digestion, highlighting a critical role of free radicals in shutting down digestion to alleviate stress and reduce food consumption.
所有生物都依赖食物消化来生存，然而调节这一过程的脑-肠信号传导机制尚未完全明确。在此，我们利用已建立的秀丽隐杆线虫消化模型，发现了一条神经元活性氧（自由基）向肠道发出信号以抑制消化的途径。基因筛选显示，减少负责维持活性氧平衡的基因会增加自由基并减少消化。嗅觉神经元（AWC）中的PRDX-2基因敲除会升高活性氧并降低消化能力，这是由神经肽NLP-1以及肠道中线粒体未折叠蛋白反应（UPR）的激活介导的。此外，过表达nlp-1或消融AWC神经元都会触发UPR并抑制消化。这些发现揭示了一种脑-肠联系，即神经元PRDX-2介导的活性氧信号传导调节食物消化，突出了自由基在停止消化以减轻压力和减少食物消耗方面的关键作用。
