# Molecular hydrogen improves obesity and diabetes by inducing hepatic FGF21 and stimulating energy metabolism in db/db mice.
> 水素水摂取によるFGF21誘導とエネルギー代謝促進を介したdb/dbマウスの肥満・糖尿病改善効果


## Abstract

Following oral administration of hydrogen-rich water (H2-water), hepatic glycogen was found to accumulate H2, providing a mechanistic basis for why even modest H2 intake can benefit various disease models. In db/db mice lacking functional leptin receptors, ad libitum H2-water consumption reduced hepatic oxidative stress and markedly ameliorated fatty liver; similar effects were observed in high-fat-diet-fed wild-type mice. Despite unchanged food and water intake, long-term H2-water drinking significantly suppressed body fat accumulation and weight gain. Plasma levels of glucose, insulin, and triglycerides were lowered to an extent comparable to dietary restriction. Gene expression profiling revealed upregulation of fibroblast growth factor 21 (FGF21), a hepatic hormone that promotes fatty acid and glucose utilization. Consistent with this, H2 exposure increased oxygen consumption, indicating enhanced energy expenditure. These findings point to a role for H2 in addressing obesity, type 2 diabetes, and metabolic syndrome.

### Mechanism

H2 accumulates in hepatic glycogen after H2-water ingestion, upregulates FGF21 expression in the liver, and thereby promotes fatty acid and glucose utilization while reducing oxidative stress and increasing overall energy expenditure.

## Bibliographic

- **Authors**: Kamimura N, Nishimaki K, Ohsawa I, Ohta S
- **Journal**: Obesity (Silver Spring)
- **Year**: 2011
- **PMID**: [21293445](https://pubmed.ncbi.nlm.nih.gov/21293445/)
- **DOI**: [10.1038/oby.2011.6](https://doi.org/10.1038/oby.2011.6)
- **Study type**: animal study
- **Delivery route**: hydrogen-rich water
- **Effect reported**: positive

## Delivery context

Hydrogen-rich water is a low-risk delivery route, but the achievable systemic hydrogen dose is bounded. For clinical applications, inhalation is the most efficient route; inhalation, however, carries explosion risk, and concentration matters (empirical LFL of 10% applies to inhalation environments; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

## Safety notes

Hydrogen-rich water is a low-risk delivery route, but the achievable systemic hydrogen dose is bounded. For clinical applications, inhalation is the most efficient route; inhalation, however, carries explosion risk, and concentration matters (empirical LFL of 10% applies to inhalation environments; 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 21293445. https://h2-papers.org/en/papers/21293445
> **Source**: PubMed PMID [21293445](https://pubmed.ncbi.nlm.nih.gov/21293445/)