分子状水素によるPGC-1α転写共活性化因子の遺伝子発現促進と脂肪酸代謝亢進
This study investigated the mechanism by which long-term H2 ingestion improves obesity and diabetes in model mice, focusing on hepatic gene expression. DNA microarray analysis of liver tissue revealed upregulation of genes associated with fatty acid and steroid metabolism, with pathway analysis identifying the PPARα signaling cascade as a key regulatory route. PGC-1α gene expression rose transiently as an early event, subsequently driving FGF21 upregulation. Experiments in cultured HepG2 cells suggested that H2 acts through 4-hydroxy-2-nonenal and Akt/FoxO1 signaling to indirectly regulate PGC-1α expression. In wild-type mice maintained on a high-fat diet, H2-water intake lowered plasma triglyceride levels and extended average lifespan. These findings indicate that H2 initiates a transcriptional cascade beginning with PGC-1α induction, leading to PPARα pathway activation and broad improvements in lipid metabolism.
H2 transiently induces PGC-1α gene expression via 4-hydroxy-2-nonenal and Akt/FoxO1 signaling, which in turn activates the PPARα pathway to upregulate FGF21 and genes governing fatty acid and steroid metabolism.
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:
https://h2-papers.org/en/papers/28721265