iScienceMar 27, 2024

Individual differences in liver disease caused by disrupted body clocks in mice

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 22, 2026

Abstract

Chronic jet-lag significantly increased the prevalence of hepatic steatosis in wild-type mice, with notable individual variations.

Individual responses to chronic jet-lag revealed marked differences in pathological progression.
Hepatic transcriptomic analysis showed dysregulation of lipid metabolism linked to chronic jet-lag exposure.
Correlations were identified between the robustness of intrinsic behavioral rhythms and gene signatures affected by chronic jet-lag.
Findings suggest that physiological indicators could serve as predictive markers for diseases related to circadian rhythm misalignment.

Simplified

Pathological consequences of circadian misalignment, such as shift work, show considerable individual differences, but the lack of mechanistic understanding hinders precision prevention to prevent and mitigate disease symptoms. Here, we employed an integrative approach involving physiological, transcriptional, and histological phenotypes to examine inter-individual differences in pre-symptomatic pathological progression, preceding irreversible disease onset, in wild-type mice exposed to chronic jet-lag (CJL). We observed that CJL markedly increased the prevalence of hepatic steatosis with pronounced inter-individual differences. Stratification of individual mice based on CJL-induced hepatic transcriptomic signature, validated by histopathological analysis, pinpoints dysregulation of lipid metabolism. Moreover, the period and power of intrinsic behavioral rhythms were found to significantly correlate with CJL-induced gene signatures. Together, our results suggest circadian rhythm robustness of the animals contributes to inter-individual variations in pathogenesis of circadian misalignment-induced diseases and raise the possibility that these physiological indicators may be available for predictive hallmarks of circadian rhythm disorders.

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Individual differences in liver disease caused by disrupted body clocks in mice

Abstract

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