# Long-term and daily use of molecular hydrogen induces reprogramming of liver metabolism in rats by modulating NADP/NADPH redox pathways.
> 長期的な水素分子の日常的摂取がNADP/NADPH酸化還元経路を介してラット肝臓代謝のリプログラミングを誘導する


## Abstract

This animal study investigated the hepatic effects of prolonged daily molecular hydrogen exposure in rats over a 6-month period. Animals received 2 hours of daily H2 exposure either via hydrogen-rich water consumption or inhalation of 4% H2 gas. Integrated transcriptomic and metabolomic analyses, combined with biochemical assays and micro-CT imaging, revealed that both delivery routes reduced hepatic lipogenesis while enhancing lipolysis, accompanied by decreases in visceral and brown adipose tissue mass and lower serum lipid levels. Pathway analyses identified alterations in amino acid metabolism and activation of purine nucleotide and carbohydrate biosynthesis pathways. Network interaction analysis of genes and metabolites identified NADP as the central regulatory hub of H2-induced metabolic reprogramming, supported by elevated activity in NADP-dependent metabolic pathways. Evidence of immune response modulation was also detected. These findings provide the first combined transcriptomic and metabolomic dataset characterizing molecular targets underlying long-term hydrogen exposure effects on liver metabolism.

### Mechanism

H2 exposure modulates hepatic metabolism primarily through NADP as a central regulatory node, suppressing lipogenesis, enhancing lipolysis, altering amino acid metabolism, and activating purine nucleotide and carbohydrate biosynthesis pathways, with additional immune response regulatory activity.

## Bibliographic

- **Authors**: Adzavon YM, Xie F, Yi Y, Jiang X, Zhang XQ, He J, et al.
- **Journal**: Sci Rep
- **Year**: 2022 (2022-03-10)
- **PMID**: [35273249](https://pubmed.ncbi.nlm.nih.gov/35273249/)
- **DOI**: [10.1038/s41598-022-07710-6](https://doi.org/10.1038/s41598-022-07710-6)
- **PMC**: [PMC8913832](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8913832/)
- **Study type**: animal study
- **Delivery route**: mixed routes
- **Effect reported**: positive
- **H2 concentration**: 4%

## Delivery context

This study combines multiple delivery routes. As a general principle, the most efficient route for routine hydrogen intake is inhalation. Inhalation carries explosion risk (empirical LFL of 10%; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

## Safety notes

This study combines multiple delivery routes. As a general principle, the most efficient route for routine hydrogen intake is inhalation. Inhalation carries explosion risk (empirical LFL of 10%; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

---

> **Cite as**: H2 Papers — PMID 35273249. https://h2-papers.org/en/papers/35273249
> **Source**: PubMed PMID [35273249](https://pubmed.ncbi.nlm.nih.gov/35273249/)