Differential Effects of Light and Dark Phase Modifications on Jet Lag Adaptability in Mice

ABSTRACT In chronobiology, shifting light/dark cycles is a common method to disrupt circadian rhythms. While the direction and magnitude of a phase shift (e.g., +6 denoting a 6‐h advanced shift) dictate the temporal change before and after the shift, little attention has been paid to the duration and relative proportion of daytime and nighttime during the shift, leading to a critical, unexamined variable in circadian research. In this study, we introduce the concepts of “L‐shift” (longer light phase on the shift day) and “D‐shift” (longer dark phase), and investigate how these variations impact the adaptability of mice to jet lag. By examining multiple phase shifts (12L vs. 12D, +6L vs. +6D, −6L vs. −6D), we demonstrate that L‐shifts not only facilitate faster adaptation but also significantly reduce the severity of sepsis in a jet lag‐sensitive lipopolysaccharide‐induced sepsis model. Further investigations with additional phase shifts at 1‐h intervals (+8 to +11) reinforced the enhanced fitness of mice under L‐shifts. Mechanistically, L‐shifts were found to increase sleep duration, thereby improving circadian entrainment, with sleep deprivation nullifying the adaptability differences between lighting protocols. These findings underscore a previously unrecognized factor in circadian biology and suggest that optimizing lighting protocols could profoundly improve adaptability to circadian disruptions. This research opens new avenues for enhancing therapeutic strategies and refining experimental designs in the field of chronobiology.