Circadian misalignment, frequently encountered in shiftwork and trans-meridian travel, disrupts the temporal coordination of physiological processes and increases susceptibility to metabolic, neurobehavioral, and inflammatory disorders. Concurrently, it has been established that high dietary intake of refined sugars poses additional risks to systemic homeostasis. This study investigates the interactive effects of prolonged circadian disruption and sustained high-sucrose intake on neurobehavioral outcomes, metabolic parameters, redox homeostasis, and hepatic integrity in adult male mice. Animals were maintained under either a stable 12 h light:12 h dark cycle or exposed to a 24-day protocol of alternating 8 h phase advances and delays that simulated chronic jetlag/shiftwork. Within each lighting condition, mice consumed either tap water or a 30 % sucrose solution, yielding four experimental groups. Behavioral assays revealed that combined exposure to circadian disruption and sucrose elicited pronounced anxiety-like phenotypes and significant increases in body weight and blood glucose levels. Histological and lipid-specific analyses revealed progressive hepatic steatosis, vacuolization, and lipid accumulation, with pathology most pronounced under combined circadian disruption and sucrose intake. Biochemical analyses showed reduced antioxidant enzyme activities, elevated blood glucose and triglyceride levels, and increased hepatic enzymes, indicating oxidative stress, metabolic disruption, and liver dysfunction. Notably, chronic jetlag alone impaired neurobehavior, redox balance, and liver health, while high sugar intake further amplified these effects. These findings underscore the translational significance of addressing both circadian disruption and dietary excess to mitigate metabolic and psychological risks in individuals exposed to irregular light schedules and high-sugar diets.
