Illuminating the Path of Circadian Rhythm Disruption: Dietary Behavior and Lipid Metabolic Changes in C. elegans

From cyanobacteria to humans, circadian rhythms (CR) exist in almost all organisms to adapt to the changing environment caused by the Earth’s self-rotation. Disruptions of this body clock (e.g., social jet-lag, shift work) lead to eating and metabolic disorders, which have a wide-ranging impact on health, with the potential to induce the development of clock-related metabolism diseases. The induction of acute circadian disruption in a C. elegans model was performed in this study to investigate essential physiological characteristics, food consumption behavior, dietary choices, and lipid metabolism. In this study, we innovatively employed a C. elegans model to induce acute circadian disruption and investigate its effects on physiological characteristics, food consumption behavior, dietary preferences, and lipid metabolism. Our findings reveal that acute CR disturbances, involving 6-hour advances or delays, significantly influence food intake, preference for high-fat diets, and lipid metabolism, leading to increased lipid accumulation. Lipidomic analysis via LC-MS identified significant changes in 25 triacylglycerides, 11 Phosphatidylcholines, and 4 phosphatidylethanolamines across the normal circadian rhythm, disrupted rhythm, and un-entrained groups (p< 0.05, VIP >1). Notably, a 6-hour delay in transitioning to a dark environment had a more pronounced impact on dietary behavior and lipid metabolism compared to a 6-hour advance, mirroring the effects of jet lag experienced by individuals traveling eastward versus westward. In other words, eastward travel induces greater disruptions in dietary behavior and lipid metabolism due to more severe circadian misalignment. Furthermore, this study provides a novel perspective on the intricate interplay between circadian biology and nutrition. By leveraging the C. elegans model, we establish a scalable platform to explore how circadian disturbances affect nutrient utilization and lipid profiles. This opens new avenues for developing targeted nutritional strategies and interventions to mitigate the adverse effects of circadian misalignment on metabolic health.