Impact of circadian rhythm disruption on biochemical parameters in mice

Disruption of circadian rhythm is common in rotating shift workers, individuals with jet lag, and people with irregular sleep schedules and contributes to metabolic diseases including obesity, type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, and hepatocellular carcinoma. To delineate early metabolic consequences of circadian disruption, we examined glucose, iron, and lipid homeostasis in a murine model of chronic jet lag. Mice were exposed to a validated protocol in which the light cycle was advanced by 8 hours every 2 days, and blood was collected at four Zeitgeber times (ZT0, ZT6, ZT12, ZT18). Jet-lagged mice displayed a progressive rise in random blood glucose toward the dark phase, whereas controls remained within the normal range with a distinct circadian pattern (p < 0.05), suggesting altered glucose regulation across day and night. Serum iron remained within normal limits and showed only minor circadian variation compared with controls (p < 0.05), indicating largely preserved iron homeostasis. In contrast, lipid metabolism was profoundly altered. Total cholesterol and triglycerides were significantly higher and exhibited phase-shifted rhythms, with exaggerated nocturnal peaks and light-phase elevations. HDL levels were consistently reduced, while LDL/VLDL showed marked increase in concentration (all p < 0.05). These patterns are consistent with disturbed hepatic lipid synthesis, export, and peripheral uptake and with increased nocturnal lipid mobilization. Correlation analysis revealed moderate positive associations of glucose with triglycerides and VLDL, a strong correlation between cholesterol and LDL, and a strong inverse correlation between triglycerides and HDL, whereas iron showed only weak relationships with metabolic traits. Together, these data indicate that chronic circadian misalignment preferentially disrupts coordinated glucose and lipid metabolism while iron levels showed modest variations, consistent with early metabolic alterations associated with circadian disruption.