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However, the role of the circadian clock throughout the entire course of sepsis remains unclear. This study aims to investigate whether the endogenous circadian clock mediates differential effects on sepsis at different stages of the disease. We induced sepsis in mice by intraperitoneal injection of lipopolysaccharide (LPS) during the rest phase (Zeitgeber Time 6, ZT6) and the active phase (ZT18). We found a significant time\u2010dependent dual effect: Mice in the ZT18 group exhibited a more intense inflammatory response in the acute phase within 24\u2009h, characterized by more severe hypothermia and elevated serum and tissue levels of tumor necrosis factor (TNF\u2010\u03b1), leading to higher acute\u2010phase mortality. However, upon extending the observation period to 5\u2009days, it was observed that ZT18 group had a higher survival rate. The long\u2010term survival advantage of the ZT18 group was associated with stronger metabolic resilience, characterized by faster recovery of the respiratory exchange ratio (RER) and energy expenditure, as well as earlier restoration of daily activity capacity. Lesioning the central clock, the suprachiasmatic nucleus (SCN), eliminated the diurnal differences in LPS\u2010induced mortality and metabolic disturbances, indicating that the phenomenon is driven by the central clock. These findings provide a new theoretical framework for developing stage\u2010specific chronotherapies for sepsis.<\/jats:p>","DOI":"10.1096\/fj.202504451rr","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T18:11:56Z","timestamp":1776190316000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Opposing Effects of the Circadian Timing on Acute and Chronic Phases of Sepsis"],"prefix":"10.1096","volume":"40","author":[{"given":"Shaoying","family":"Lan","sequence":"first","affiliation":[{"name":"School of Life Sciences and Medical Engineering Anhui University  Hefei Anhui Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangting","family":"Lang","sequence":"additional","affiliation":[{"name":"School of Life Sciences and Medical Engineering Anhui University  Hefei Anhui Province 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