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. HighlightsO_LIAnimals govern PC level to regulate lipid homeostasis in response to diets C_LIO_LIB12 regulates SAM-PC axis to affect lipogenic genes expression and LD biogenesis C_LIO_LICoelomocytes regulate diets-induced lipid homeostasis through asm-3 C_LIO_LIasm-3 constructs a positive feedback loop to participate in PC metabolism C_LI