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ORIGINAL RESEARCH article

Front. Cell Dev. Biol.

Sec. Molecular and Cellular Reproduction

Volume 13 - 2025 | doi: 10.3389/fcell.2025.1622695

High-glucose diets modulate phosphatidylcholine metabolism to varying Caenorhabditis elegans fecundity

Provisionally accepted
Chao-Wen  WangChao-Wen Wang1,2*Phebe  ChiuPhebe Chiu2Sophia  MonsalveiSophia Monsalvei3Ricardo  RoureRicardo Roure3Xiaofei  BaiXiaofei Bai3Jia-Jin  LawJia-Jin Law2Yu- Ching  WuYu- Ching Wu2Yet-Ran  ChenYet-Ran Chen4You-Liang  ChengYou-Liang Cheng5Rey-Huei  ChenRey-Huei Chen5Yi-Chun  WuYi-Chun Wu6
  • 1Department of Life Sciences, National Cheng Kung University, Tainan, Taiwan
  • 2Institute of Plant and Microbial Biology, Academia Sinica, Taipei, Taiwan
  • 3Department of Biology and Genetics Institute, University of Florida, Gainesville, United States
  • 4Institute of Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan
  • 5Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan
  • 6Institute of Molecular and Cellular Biology, National Taiwan University, Taipei, Taiwan

The final, formatted version of the article will be published soon.

Diet represents a dynamic facet of life, pivotal for understanding how animals respond to dietary cues and adjust their metabolism and physiology. Caenorhabditis elegans fed high-glucose Escherichia coli OP50 diet experience a decline in fecundity. These animals exhibit altered lipid homeostasis, marked by reduced monounsaturated and elevated cyclopropane fatty acids, along with an overall decrease in phosphatidylcholine (PC) and an increase in triacylglycerols. This is accompanied by abnormal lipid droplet and vitellogenin accumulation in their intestine and oocytes. By contrast, C. elegans fed a high-glucose Comamonas aquatica DA1877 diet maintain lipid homeostasis and show normal fecundity. We identified a strong correlation between altered lipid homeostasis and reproductive decline and found that dietary signals derived from C. aquatica DA1877 protect against high-glucose toxicity. Further investigation revealed that high-glucose diets may rewire the choline-methionine metabolic axis, leading to reduced PC levels, which contributes to decreased fecundity. Additionally, PC depletion is accompanied by diminished RAS/ERK signaling in both germline and somatic sheath cells, resulting in impaired oocyte production. Notably, vitamin B12 supplementation restores this signaling pathway and rescues the diet-specific reproduction defect under high-glucose condition, suggesting a genetic network linking lipid homeostasis and signaling is modulated by dietary cues under high glucose conditions, ultimately impacting fecundity.

Keywords: Glucose, Diet, Phosphatidylcholine, triacylglycerol, Choline, Methionine, Vitamin B12, omics

Received: 04 May 2025; Accepted: 30 Jul 2025.

Copyright: © 2025 Wang, Chiu, Monsalvei, Roure, Bai, Law, Wu, Chen, Cheng, Chen and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Chao-Wen Wang, Department of Life Sciences, National Cheng Kung University, Tainan, Taiwan

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