HormonesMelatonin

Chronic photoperiod disruption impairs hepatic protein-synthetic function, which is fully restored by exogenous melatonin in rats

Constant light exposure for 21 days reduced albumin levels by 15.7% in male and 15.9% in female rats, and suppressed BMAL1 and CLOCK expression by over 70% while increasing PER2. Melatonin treatment (12 mg/L in drinking water) fully restored all circadian protein expression and normalized protein synthesis parameters to control levels in both sexes.

Last updated: Jul 8, 2026โ€ข0 RCTsโ€ข๐Ÿ“– Read as article โ†’

Evidence Score

Evidence Score26/100
Human RCTโ˜†โ˜†โ˜†โ˜†โ˜†
Meta-analysisโ˜†โ˜†โ˜†โ˜†โ˜†
Mechanismโ˜…โ˜…โ˜…โ˜…โ˜…
Safetyโ˜…โ˜…โ˜…โ˜…โ˜†
Confidencelow

Study Evidence

Study 1. Circadian dysregulation as a factor in impaired hepatic protein-synthetic function under chronic photoperiod disruption: the role of sex and chronobiotic correction.

observational

Areshidze DA, Kozlova MA, Anurkina AI, Chernikov VP, Gladyshev NS ยท Biology of sex differences (2026)

Participants: N/A
Duration: 21 days
Intervention: Constant light (LL) for 21 days with or without melatonin (12 mg/L in drinking water)
Outcome: Plasma total protein and albumin levels; percentage of hepatocytes positive for BMAL1, CLOCK, and PER2
Effect Size: Albumin reduction: 15.7% (males), 15.9% (females); BMAL1/CLOCK reduction >70%; PER2 increase 28.9-35.0%; BMAL1-albumin correlation r=0.79-0.81
Population: 240 adult Wistar rats (120 males, 120 females)

Result:

Mechanism Graph

Constant light disrupts circadian clock gene expression in the liver
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BMAL1 and CLOCK expression are suppressed by over 70%
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PER2 expression paradoxically increases by 28.9-35.0%
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These changes are strongly correlated with reduced albumin production, indicating impaired hepatic protein synthesis

Limitations

  • โš Animal model (rats) limits direct generalizability to humans
  • โš Only one type of circadian disruption (constant light) was tested; other forms of desynchronosis may yield different results

Frequently Asked Questions

What is the main finding of this study?โ–ผ

Chronic exposure to constant light disrupts liver clock proteins (BMAL1, CLOCK, PER2) and reduces albumin production by about 16% in both male and female rats. Melatonin treatment fully reverses these effects.

How does melatonin affect liver function under circadian disruption?โ–ผ

Melatonin (12 mg/L in drinking water) fully restored the expression of BMAL1, CLOCK, and PER2 and normalized total protein and albumin levels to control values in both sexes.

Is there a sex difference in response to circadian disruption?โ–ผ

Yes, two-way ANOVA showed a significant interaction between lighting conditions and sex (F=7.2, p<0.05), indicating sexual dimorphism in susceptibility to desynchronosis.

Can BMAL1 be used as a marker for liver problems?โ–ผ

Yes, BMAL1 expression was the strongest independent predictor of albumin levels (ฮฒ=0.52, p<0.0001) and showed high predictive performance for hypoalbuminemia (AUC=0.87-0.89).

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References

  1. 1.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. PMID: 42401921 DOI: 10.1186/s13293-026-00949-y
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