Twenty-one days of constant light suppresses liver protein production by roughly 16% and decimates key circadian clock proteins, but the hormone melatonin fully reverses the damage in both sexes, according to a study published July 4 in Biology of Sex Differences.
The findings carry direct implications for shift workers, frequent long-haul travelers, and anyone living under disrupted light cycles. The liver’s protein-synthetic machinery, including the production of albumin, a critical blood protein, runs on a daily rhythm orchestrated by the circadian clock. When that clock goes silent, the machinery falters.
What they found
The research team, led by David A. Areshidze, exposed 240 adult Wistar rats (120 males, 120 females) to three conditions: a normal light-dark cycle, constant light for 21 days (dark deprivation), or constant light plus melatonin in their drinking water (12 mg/L).
Constant light produced striking molecular and metabolic changes:
- Albumin levels dropped by 15.7% in males and 15.9% in females, indicating impaired hepatic protein synthesis.
- Clock proteins BMAL1 and CLOCK decreased by more than 70% in liver cells of both sexes.
- PER2, a repressor component of the clock, paradoxically increased by 28.9-35.0%, a signature of desynchronosis where core clock components fall out of alignment.
- Two-way ANOVA confirmed significant effects of lighting condition (F = 145.3, p < 0.0001), sex (F = 18.7, p < 0.01), and their interaction (F = 7.2, p < 0.05).
Critically, albumin levels correlated strongly with clock protein expression: BMAL1 (r = 0.79-0.81, p < 0.001), CLOCK (r = 0.69-0.74, p < 0.001), and PER2 (r = -0.68 to -0.71, p < 0.001). ANCOVA identified BMAL1 expression as the single strongest predictor of albumin levels (beta = 0.52, p < 0.0001), with sex retaining independent significance (p = 0.02). ROC analysis showed BMAL1 expression could predict hypoalbuminemia with AUC values of 0.87-0.89.
Melatonin fully restored every parameter. The treatment normalized BMAL1, CLOCK, and PER2 expression and brought total protein and albumin levels back to control values in both male and female rats.
Why it matters
The liver depends on circadian timing to schedule its metabolic functions, including protein synthesis. This study shows that the connection is bidirectional and quantifiable: photoperiod disruption suppresses specific clock proteins, and those changes directly track with functional output (albumin levels).
The sex differences are notable. The interaction between lighting condition and sex suggests that males and females may have different sensitivities to circadian disruption, a factor rarely accounted for in shift work health studies. BMAL1 emerged as a potential biomarker for circadian-related liver dysfunction, with strong predictive power for hypoalbuminemia.
Melatonin’s restorative effect across both sexes positions it as a potential chronobiotic intervention for populations with unavoidable circadian disruption, night shift workers, ICU staff, and individuals with non-24-hour lifestyles.
Limits
This is an animal study. Rat circadian physiology is nocturnal, and the magnitude of melatonin’s effect and the dosing regimen (12 mg/L in drinking water) may not translate directly to humans. The constant-light model represents an extreme form of circadian disruption unlikely to match real-world shift work schedules.
Bottom line
Chronic light-based circadian disruption damages the liver’s ability to produce proteins by degrading its clock machinery. Melatonin, an endogenous hormone already used clinically for sleep disorders, fully reverses this damage in rats, opening a potential chronobiotic strategy for protecting liver function in people with disrupted light cycles.
Source: Areshidze DA, Kozlova MA, Anurkina AI, Chernikov VP, Gladyshev NS. Circadian dysregulation as a factor in impaired hepatic protein-synthetic function under chronic photoperiod disruption: the role of sex and chronobiotic correction. Biology of Sex Differences. 2026 Jul 4. DOI: 10.1186/s13293-026-00949-y. PMID: 42401921.