Molecular hydrogen stimulates the gene expression of transcriptional coactivator PGC-1α to enhance fatty acid metabolism

Abstract

We previously reported that molecular hydrogen (H2) acts as a novel antioxidant to exhibit multiple functions. Moreover, long-term drinking of H2-water (water infused with H2) enhanced energy expenditure to improve obesity and diabetes in db/db mice accompanied by the increased expression of fibroblast growth factor 21 (FGF21) by an unknown mechanism. H2 was ingested by drinking of H2-water or by oral administration of an H2-producing material, MgH2. The comprehensive gene expression profile in the liver of db/db mice was analyzed by DNA microarray. The molecular mechanisms underlying the gene expression profile was investigated using cultured HepG2 cells. Moreover, the effects on lifespan of drinking H2-water were examined using wild-type mice that were fed a fatty diet. Pathway analyses based on comprehensive gene expression revealed the increased expression of various genes involved in fatty acid and steroid metabolism. As a transcription pathway, the PPARα signaling pathway was identified to upregulate their genes by ingesting H2. As an early event, the gene expression of PGC-1α was transiently increased, followed by increased expression of FGF21. The expression of PGC-1α might be regulated indirectly through sequential regulation by H2, 4-hydroxy-2-nonenal, and Akt/FoxO1 signaling, as suggested in cultured cell experiments. In wild-type mice fed the fatty diet, H2-water improved the level of plasma triglycerides and extended their average of lifespan. H2 induces expression of the PGC-1α gene, followed by stimulation of the PPARα pathway that regulates FGF21, and the fatty acid and steroid metabolism.

Hydrogen gas restores exhausted CD8+ T�cells in patients with advanced colorectal cancer to improve prognosis

“…Molecular hydrogen was reported to activate PGC-1α (28), which enhances mitochondrial activity (29), thereby rescuing exhausted CD8 + T cells with inactive mitochondria following progressive loss of PGC-1α (15). Therefore, the present study investigated whether hydrogen gas alters the proportion of PD- CD8 + T cell ratio was found to be an independent predictor of poor PFS (HR, 6.459; 95% CI, 2.384-17.50; P<0.0001) and OS (HR, 2.957; 95% CI, 1.185-7.378; P=0.020).…”

“…It was recently reported that exhausted CD8 + T cells exhibit mitochondrial dysfunction, caused by the inactivation of PGC-1α, to express immune checkpoint inhibitors such as PD-1 and Tim-3, but return to the active effector state following exposure to certain stimulants (7). Hydrogen was recently reported to stimulate PGC-1α (28), which enhances mitochondrial function (29) and thus may rescue exhausted CD8 + T cells. The present study found that hydrogen gas reduced the proportion of all four PD-1 + CD8 + T cell subsets and increased the proportions of all four PD-1 -CD8 + subsets.…”

“…There are several studies on the preventive and therapeutic effects of hydrogen on various diseases, including cancer (25)(26)(27). Notably, it was reported that molecular hydrogen activates PGC-1α (28), which is a positive regulator of mitochondrial biogenesis and respiration, adaptive thermogenesis, gluconeogenesis and a number of…”

<p>The Effects of 24-Week, High-Concentration Hydrogen-Rich Water on Body Composition, Blood Lipid Profiles and Inflammation Biomarkers in Men and Women with Metabolic Syndrome: A Randomized Controlled Trial</p>

“…1 Molecular hydrogen modulates signal transduction, protein phosphorylation cascades, gene expression, autophagy, miRNA expression, as well as has important metabolic effects. 5,6 H 2 can induce the Keap1/Nrf2 signaling pathway, 7 promote mitochondrial biogenesis, 8 and the cytoprotective mitochondrial unfolded protein response. 9 H 2 has been proposed to act as an exercise mimetic and redox adaptogen via activating hormetic pathways.…”

Effects of Hydrogenized Water on Intracellular Biomarkers for Antioxidants, Glucose Uptake, Insulin Signaling and SIRT 1 and Telomerase Activity

“…The level of total Akt has also been measured in a number of cellular studies and shown remaining unchanged throughout the study (Data not shown). A previous study reported that H 2 suppressed lipid peroxidation, resulting in a decrease in its end-product, 4hydroxy-2noneal (4HNE), and that 4-HNE modified Akt activation [26]. Thus it is possible the H2 indirectly contributes to insulin signaling [25].…”