Chicoric Acid Differentially Ameliorates Circadian Rhythm Disorder-Induced Liver Glucose Homeostasis Dysregulation in Mice Depending on Intervention Time

Dietary phenolic compounds have demonstrated significant potential in preventing shift-work-induced metabolic dysregulation. Meanwhile, chrononutrition has revealed that the intake time of these compounds is closely related to human health. This study explored the effects and potential mechanism of the intervention time of chicoric acid on the improvement of glucose metabolism in a mouse model of the circadian rhythm disorder. Results showed that CA was effective in improving glucose tolerance and restoring the expression levels and phase shifts of clock genes (Bmal1, Per2, Cry2, etc.) and glucose metabolism-related genes (Gck, Pepck, G6pc). Further silencing of Bmal1 in HepG2 cells revealed that CA can act as a biological clock regulator that regulates glucose metabolism-related genes in a Bmal1-dependent manner. Furthermore, we found that CA intervention at ZT12 optimally promoted glucose metabolic homeostasis, and the possible mechanism was that the intervention time coincided with the high expression of Bmal1.