Work

Integrative transcriptomics and metabolomics reveal Cry1-associated hepatic alterations and plasma essential fatty acids as biomarkers of residual circadian disruption post-sepsis

Year: 2026

Type: article

Abstract: Background: Sepsis disrupts circadian rhythm, leaving lasting molecular traces and circadian insensitivity to jet lag even after acute phase recovery. However, the core mechanism and biomarkers of residual circadian dysfunction post-sepsis remain unclear, which hinders targeted interventions. Methods: Male mice were subjected to non-lethal LPS injection, and after 7 days of recovery, liver transcriptomics and plasma metabolomics were integrated. Behavioral, physiological, and molecular analyses were performed, with statistical tests including DESeq2, Student's t-test, MetaCycle, and ROC curve analysis. Results: Significant transcriptomic alterations were observed, most prominently at Zeitgeber time 21. Linoleic acid (LA) and alpha-linolenic acid (ALA) were identified as sampling-time-independent candidate biomarkers associated with post-sepsis circadian disruption. Exogenous supplementation of these two fatty acids shortened male mice's rhythm re-entrainment period. Conclusions: -essential fatty acid axis potentially contributing to post-sepsis circadian dysfunction based on multi-omics associations, providing novel biomarkers and a metabolic intervention strategy for detecting and treating circadian rhythm disorders in sepsis survivors.

Source: Frontiers in Endocrinology

DOI: 10.3389/fendo.2026.1916119