Dietary bacteria controls C. elegans lipid metabolism through pathways converging at phosphatidylcholine

Dietary factors play a pivotal role in regulating metabolism in both health and disease. Lipid metabolism is particularly important for organismal health and longevity. However, the mechanisms by which dietary factors influence lipid metabolism remain poorly understood. Here, using the nematode C. elegans as a model system, we investigated the influence of distinct bacterial diets on fat metabolism. We found that dietary vitamin B12 activates the S-adenosyl methionine (SAM) and phosphatidylcholine (PC) biosynthetic pathways. This activation leads to elevated levels of PC, which in turn suppresses the expression of the gene fat-7 and modulates lipid droplet dynamics through the regulatory proteins SBP-1/SREBP1 and SEIP-1/SEIPIN, respectively. Additionally, we identified a feedback loop involving SBP-1-mediated regulation of acid sphingomyelinase ASM-3, which enhances the production of phospho-choline and further stimulates PC synthesis. Our localization studies further suggest that ASM-3 may act as a signaling mediator between the intestine and coelomocytes, coordinating their roles in vitamin B12-mediated fat regulation. Overall, our findings shed new light on the complex interplay between diet and metabolic regulation, with a particular emphasis on the central role of phosphatidylcholine. To understand the mechanism underlying the regulation of host lipid content triggered by different bacteria diets, we examined the gene expression changes elicited by the two different bacterial diets in young adult animals by RNA-seq. Overall design: Comparative gene expression profiling analysis of RNAseq data from worms feeding DA1877 or OP50 diet.

饮食因素在健康与疾病状态下均对代谢调控发挥关键作用，其中脂质代谢对生物体健康与寿命尤为重要。然而，饮食因素影响脂质代谢的具体分子机制仍有待阐明。本研究以秀丽隐杆线虫（Caenorhabditis elegans，C. elegans）为模式生物体系，探究了不同细菌饮食对脂肪代谢的影响。研究发现，饮食中的维生素B12可激活S-腺苷甲硫氨酸（S-adenosyl methionine，SAM）与磷脂酰胆碱（phosphatidylcholine，PC）的生物合成通路；该激活过程可提升PC水平，进而抑制脂肪代谢相关基因fat-7的表达，并分别通过调控蛋白SBP-1/SREBP1与SEIP-1/SEIPIN调节脂滴动态变化。此外，本研究还鉴定出一条由SBP-1介导调控酸性鞘磷脂酶（acid sphingomyelinase）ASM-3的反馈通路，该通路可促进磷酸胆碱的生成并进一步刺激PC合成。定位研究进一步表明，ASM-3可作为肠道与体腔细胞间的信号介导因子，协调二者在维生素B12介导的脂肪调控中的功能。综上，本研究结果为饮食与代谢调控间的复杂互作关系提供了新见解，尤其凸显了磷脂酰胆碱的核心调控作用。为阐明不同细菌饮食诱导宿主脂质含量变化的调控机制，本研究通过RNA测序（RNA-seq）分析了年轻成虫在喂食两种不同细菌饮食后的基因表达变化。实验整体设计：对喂食DA1877或OP50饮食的线虫的RNA测序数据开展比较基因表达谱分析。