Transcriptomic and Metabolomic Signatures of Acute Circadian Misalignment in Mice

ABSTRACT Acute circadian misalignment, such as that induced by a single episode of jet lag, can leave molecular traces even after behavioral rhythms appear to recover. Here, we applied an integrated multi‐omics approach—combining liver transcriptomics and plasma metabolomics—to characterize residual signatures on the 7th day after a single 6‐h phase advance in male mice. Our data revealed significant alterations, particularly in the core clock genes Bmal1 and Cry1 , and the metabolites l ‐arginine and SM(d18:1/18:1(11Z)), with notable differences at Zeitgeber Time 0 (ZT0). Additionally, we identified l ‐Serine as a potential biomarker for circadian misalignment, independent of sampling time. These findings provide new insights into potential biomarkers for detecting acute circadian misalignment.