Wang Chao-Wen, Chiu Phebe, Monsalve Sophia, Roure Ricardo, Bai Xiaofei, Law Jia-Jin, Wu Yu-Ching, Chen Yet-Ran, Cheng You-Liang, Chen Rey-Huei, Wu Yi-Chun
Department of Life Sciences, National Cheng Kung University, Tainan, Taiwan.
Institute of Plant and Microbial Biology, Academia Sinica, Taipei, Taiwan.
Front Cell Dev Biol. 2025 Aug 29;13:1622695. doi: 10.3389/fcell.2025.1622695. eCollection 2025.
fed a high-glucose Escherichia coli OP50 diet exhibit reduced fecundity, but the underlying mechanisms remain unclear.
A differential high-glucose diet paradigm was established using fed two bacterial diets that produced distinct fecundity outcomes under high-glucose conditions. The effects of these diets in varying conditions were analyzed through transcriptomic, lipidomic, and metabolomic profiling to correlate with fecundity. Supplementation experiments were further performed to validate the links between changes in lipid metabolism and fecundity. By characterizing the gerlime phenotypes, we constructed a model to interpret how dietary inputs alter oogenesis signaling and, consequently, fecundity outcomes.
fed a high-glucose OP50 diet exhibit reduced fecundity, accompanied by disrupted lipid homeostasis characterized by decreased monounsaturated and increased cyclopropane fatty acids, reduced phosphatidylcholine and elevated triacylglycerols, and abnormal lipid droplet and vitellogenin accumulation in the intestine and oocytes. In contrast, worms fed a high-glucose DA1877 diet maintain lipid balance and normal fecundity. We identified altered lipid metabolism strongly correlated with reproductive decline, whereas dietary signals from protected against glucose toxicity. Mechanistically, high-glucose diets appeared to rewire the choline-methionine axis, lowering PC levels and reducing RAS/ERK signaling in germline and gonadal sheath cells, thereby impairing oogenesis. Notably, vitamin B12 supplementation restored RAS/ERK signaling and rescued the diet-specific fecundity defects.
We demonstrate that dietary cues under high-glucose conditions modulate a genetic network linking lipid homeostasis and signaling pathways, ultimately determining fecundity outcomes in .
喂食高糖大肠杆菌OP50饮食的线虫繁殖力降低，但其潜在机制仍不清楚。
建立了一种差异化高糖饮食模式，使用两种细菌饮食，它们在高糖条件下产生不同的繁殖力结果。通过转录组学、脂质组学和代谢组学分析来研究这些饮食在不同条件下的作用，以与繁殖力相关联。进一步进行补充实验以验证脂质代谢变化与繁殖力之间的联系。通过表征线虫表型，我们构建了一个模型来解释饮食输入如何改变卵子发生信号传导，进而影响繁殖力结果。
喂食高糖OP50饮食的线虫繁殖力降低，同时伴随着脂质稳态的破坏，其特征为单不饱和脂肪酸减少、环丙烷脂肪酸增加、磷脂酰胆碱减少、三酰甘油升高，以及肠道和卵母细胞中脂滴和卵黄蛋白原积累异常。相比之下，喂食高糖DA1877饮食的线虫维持脂质平衡和正常繁殖力。我们发现脂质代谢改变与生殖能力下降密切相关，而来自DA1877的饮食信号可防止葡萄糖毒性。从机制上讲，高糖饮食似乎重新调整了胆碱 - 蛋氨酸轴，降低了磷脂酰胆碱水平并减少了生殖系和性腺鞘细胞中的RAS/ERK信号传导，从而损害卵子发生。值得注意的是，补充维生素B12可恢复RAS/ERK信号传导并挽救特定饮食的繁殖力缺陷。
我们证明，高糖条件下的饮食线索调节了一个连接脂质稳态和信号通路的遗传网络，最终决定了线虫的繁殖力结果。
