What question did this study set out to answer?

This research aims to explore the bidirectional relationship between insomnia and metabolites using human and mouse data.

May 26, 2026Metabolomics0 citationsOpen Access

Causal relationships between insomnia and blood metabolome: a Mendelian randomization study with mouse experimental validation

HFHsien‐Yu Fan CHCheng-Chia Hsieh TCTsung-Po Chen

Key Points

This research aims to explore the bidirectional relationship between insomnia and metabolites using human and mouse data.
Analyzed data from two genome-wide association studies involving 336,965 participants for insomnia and 7,824 for metabolites.
Conducted mouse experiments with 12 mice divided into control and chronic sleep deprivation groups for 32 days, analyzing blood and fecal metabolites.
Examined genetic variants associated with both insomnia and metabolite levels.
Higher oleate levels were associated with a reduced risk of insomnia (β: -5.99, p = 0.01).
Insomnia led to increased levels of glucose (β: 0.18, p = 0.002) and mannose (β: 0.11, p = 0.02), along with changes in six lipids and four amino acids.
Chronic sleep deprivation in mice resulted in lower corticosterone levels (p = 0.03) and increased glucose and mannose (p = 0.001).

Abstract

BACKGROUND: The two-way relationship between metabolites and insomnia is not yet fully understood. OBJECTIVE: We investigated the bidirectional relationship between metabolites and insomnia using human genome-wide association study and mouse models to identify potential biomarkers. METHODS: We analyzed data from two large genome-wide association studies: one on insomnia (336,965 participants) and one on metabolites (7,824 participants). Genetic variants related to metabolites and insomnia were examined. In the animal study, 12 mice were divided into control and chronic sleep deprivation groups (n = 6 each). After 32 days, blood and fecal metabolites were analyzed. RESULTS: Higher oleate levels were linked to lower insomnia risk (β: -5.99, p = 0.01), but insomnia did not alter oleate levels. Insomnia increased glucose (β: 0.18, p = 0.002), mannose (β: 0.11, p = 0.02), and influenced six lipids and four amino acids. In mice, sleep deprivation lowered corticosterone (p = 0.03), raised glucose and mannose (p = 0.001), and reduced blood (p = 0.007) and fecal oleate (p = 0.05). Fecal 4-aminobutyric acid also decreased (p = 0.01). CONCLUSIONS: Insomnia and metabolites exhibited a bidirectional relationship, with notable metabolic and hormonal changes in the animal model. Improving sleep hygiene and regular assessments may help mitigate insomnia-related metabolic disruptions.

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