Long‑term and daily use of molecular hydrogen induces reprogramming of liver metabolism in rats by modulating NADP/NADPH redox pathways

Abstract

Molecular hydrogen (H2) 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 H2 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 H2 on liver function. Rats exposed 2 h daily to H2 either by drinking HRW (H2 dissolved in H2O) or by breathing 4% H2 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 H2-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 H2 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 H2. 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.

Study details

Article type

Original Research

Disease / injury model

None (Healthy rats)

Duration

6 months

Dose comparison

The study compares the effects of two delivery routes (HRW >800 µM, HI 4% H2) but does not directly compare different concentrations within each method.

Dose-dependent effect

No

Outcome

Positive

Findings

Long-term and daily use of molecular hydrogen in healthy rats induces reprogramming of liver metabolism, characterized by reduced lipogenesis, enhanced lipolysis, loss of visceral fat and brown adipose tissue, reduced serum lipids, altered amino acid metabolism, and activation of purine nucleotide and carbohydrate biosynthesis pathways. NADP is identified as a central regulator of these metabolic alterations.