Faculty of Environment and Life, Beijing University of Technology, Beijing, 100124, People's Republic of China.
Beijing Molecular Hydrogen Research Center, Beijing, 100124, People's Republic of China.
Sci Rep. 2022 Mar 10;12(1):3904. doi: 10.1038/s41598-022-07710-6.
Molecular hydrogen (H) has emerged as a new therapeutic option in several diseases and is widely adopted by healthy people. However, molecular data to support therapeutic functions attributed to the biological activities of H remain elusive. Here, using transcriptomic and metabolomic approaches coupled with biochemistry and micro-CT technics, we evaluated the effect of long-term (6 months) and daily use of H on liver function. Rats exposed 2 h daily to H either by drinking HRW (H dissolved in HO) or by breathing 4% H gas showed reduced lipogenesis and enhanced lipolysis in the liver, which was associated with apparent loss of visceral fat and brown adipose tissue together with a reduced level of serum lipids. Both transcripts and metabolites enriched in H-treated rats revealed alteration of amino acid metabolism pathways and activation of purine nucleotides and carbohydrate biosynthesis pathways. Analysis of the interaction network of genes and metabolites and correlation tests revealed that NADP is the central regulator of H induced metabolic alterations in the liver, which was further confirmed by an increase in the level of components of metabolic pathways that require NADP as substrate. Evidence of immune response regulation activity was also observed in response to exposure to H. This work is the first to provide metabolomic and transcriptomic data to uncover molecular targets for the effect of prolonged molecular hydrogen treatment on liver metabolism.
氢气（H）已成为多种疾病的新治疗选择，并且受到健康人群的广泛采用。然而，支持归因于 H 的生物学活性的治疗功能的分子数据仍然难以捉摸。在这里，我们使用转录组学和代谢组学方法，结合生物化学和微 CT 技术，评估了长期（6 个月）和日常使用 H 对肝功能的影响。每天通过饮用 HRW（溶解在 HO 中的 H）或呼吸 4%H 气体暴露 2 小时的大鼠显示肝脏中脂肪生成减少和脂肪分解增强，这与内脏脂肪和棕色脂肪组织明显减少以及血清脂质水平降低有关。在 H 处理的大鼠中丰富的转录本和代谢物揭示了氨基酸代谢途径的改变以及嘌呤核苷酸和碳水化合物生物合成途径的激活。基因和代谢物相互作用网络的分析和相关测试表明，NADP 是 H 诱导肝脏代谢改变的中央调节剂，这通过代谢途径需要 NADP 作为底物的成分水平的增加进一步得到证实。还观察到对暴露于 H 的免疫反应调节活性的证据。这项工作首次提供了代谢组学和转录组学数据，以揭示长期分子氢处理对肝脏代谢影响的分子靶标。
