Integrative transcriptomics and metabolomics reveal Cry1-associated hepatic alterations and plasma essential fatty acids as biomarkers of residual circadian disruption post-sepsis
- 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University , ,
- 2National Local Joint Engineering Research Center for Precision Surgery and Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, The First Affiliated Hospital of Xi’an Jiaotong University , ,
- 3Department of Cell Biology and Physiology, The University of Kansas Medical Center , , ,
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: This study identifies a hypothesized Cry1 -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.
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BibTeX
@article{zhao2026integrative,
title = {{Integrative transcriptomics and metabolomics reveal Cry1-associated hepatic alterations and plasma essential fatty acids as biomarkers of residual circadian disruption post-sepsis}},
author = {Junzhou Zhao and Tianxiao Huang and Li Wang and Yun Shi and Wanni Zou and Yunxuan Chen and Qisheng Su and Linlan Qiao and Zheng Wu and Yi Lv and Yuanyuan Zhang and Rongqian Wu},
journal = {Frontiers in endocrinology},
year = {2026},
month = oct,
doi = {10.3389/fendo.2026.1916119},
url = {https://europepmc.org/article/PMC/PMC13668567},
note = {CC BY},
}
RIS
TY - JOUR
TI - Integrative transcriptomics and metabolomics reveal Cry1-associated hepatic alterations and plasma essential fatty acids as biomarkers of residual circadian disruption post-sepsis
AU - Junzhou Zhao
AU - Tianxiao Huang
AU - Li Wang
AU - Yun Shi
AU - Wanni Zou
AU - Yunxuan Chen
AU - Qisheng Su
AU - Linlan Qiao
AU - Zheng Wu
AU - Yi Lv
AU - Yuanyuan Zhang
AU - Rongqian Wu
PY - 2026
DA - 2026/10/01
JO - Frontiers in endocrinology
DO - 10.3389/fendo.2026.1916119
UR - https://europepmc.org/article/PMC/PMC13668567
AB - 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: This study identifies a hypothesized Cry1 -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.
SN - 1664-2392
ER -