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AdipoRon treatment partially reverses chronic sleep restriction-induced alterations in hypothalamic clock-gene expression, oxidative stress, and SIRT1/NRF2/HO-1 signaling in male mice

In male mice subjected to 21 days of chronic sleep restriction (18h/day), AdipoRon (10 μg intranasal daily) partially reversed CSR-associated changes in clock-gene expression (Clock, Bmal1, Per1, Cry1), attenuated oxidative stress, reduced LDL and ALT levels, and increased expression of SIRT1/NRF2/HO-1 pathway proteins. CSR alone increased oxidative stress and reduced SIRT1/NRF2/HO-1 expression, while AdipoRon mitigated these effects.

Last updated: Aug 20, 2026•0 RCTs•📖 Read as article →

Evidence Score

Evidence Score24/100
Human RCT☆☆☆☆☆
Meta-analysis☆☆☆☆☆
Mechanism★★★★★
Safety★★★★☆
Confidencelow

Study Evidence

Study 1. AdipoRon treatment modulates hypothalamic clock-gene expression, oxidative stress, and SIRT1/NRF2/HO-1-related signaling in male mice subjected to chronic sleep restriction.

observational

Mansouri B, Alipour MR, Mohaddes G, Malaei B, Hamidi N, Hesami-Shabestari R, Hosseinkhani M, Farajdokht F · Brain research (2026)

Participants: N/A
Duration: 21 days
Intervention: Intranasal AdipoRon (10 μg daily for 21 days) compared to control and melatonin (40 μg) groups
Outcome: Hypothalamic clock-gene expression (Clock, Bmal1, Per1, Cry1), oxidative stress markers (MDA, SOD, GPx, TAC), SIRT1/NRF2/HO-1 protein expression, serum lipid profile (triglycerides, LDL), liver enzymes (AST, ALT)
Effect Size: N/A
Population: Male mice (strain not specified in abstract)

Result:

PubMed: 42556768DOI: 10.1016/j.brainres.2026.150484

Mechanism Graph

Chronic sleep restriction induces oxidative stress in the hypothalamus
↓
CSR downregulates SIRT1/NRF2/HO-1 pathway proteins
↓
AdipoRon activates adiponectin receptors, upregulating SIRT1/NRF2/HO-1 signaling
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This reduces oxidative stress and partially normalizes clock-gene expression, mitigating metabolic disturbances

Limitations

  • ⚠Animal study; results may not directly translate to humans
  • ⚠Only male mice were used; sex-specific effects not examined
  • ⚠Mechanistic details of AdipoRon's action on clock genes not fully elucidated
  • ⚠No behavioral or functional outcomes reported (e.g., sleep quality, cognitive performance)

Frequently Asked Questions

What is AdipoRon?▼

AdipoRon is an orally active synthetic agonist of adiponectin receptors (AdipoR1 and AdipoR2), mimicking the effects of adiponectin, including activation of AMPK and PPAR-α pathways.

How does chronic sleep restriction affect the hypothalamus?▼

Chronic sleep restriction disrupts circadian clock-gene expression, increases oxidative stress, and reduces SIRT1/NRF2/HO-1 signaling, contributing to metabolic disturbances.

What dose of AdipoRon was used in this study?▼

The study used intranasal AdipoRon at a dose of 10 μg per mouse daily for 21 days.

Could AdipoRon be a potential treatment for sleep deprivation effects in humans?▼

This is an animal study; while results are promising, further research is needed to determine safety and efficacy in humans.

Products

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References

  1. 1.Mansouri B, Alipour MR, Mohaddes G, Malaei B, Hamidi N, Hesami-Shabestari R, Hosseinkhani M, Farajdokht F. "AdipoRon treatment modulates hypothalamic clock-gene expression, oxidative stress, and SIRT1/NRF2/HO-1-related signaling in male mice subjected to chronic sleep restriction.." Brain research, 2026. PMID: 42556768 DOI: 10.1016/j.brainres.2026.150484
Disclaimer: This content is for educational purposes only and is not medical advice. Evidence scores reflect the quality and quantity of available research, not clinical recommendations. Always consult a healthcare professional before starting any supplement or intervention.