Hydrogen influences HDL-associated enzymes and reduces oxidized phospholipids levels in rats fed with a high-fat diet.

Aims: Oxidized phospholipids (OxPLs) are formed as a result of oxidative stress, which potentially mediate multiple pathological effects. We aimed to evaluate the effects of hydrogen (H) on OxPLs in vivo and the underlying mechanism.

Main Methods: Rats were randomly assigned to three groups: control group fed with a chow diet, model group fed with a high-fat diet, and H-treated group fed with a high-fat diet and treated by 4% H inhalation for ten weeks. OxPLs in liver and plasma were analyzed by liquid chromatography-mass spectrometry. High-density lipoprotein (HDL) was separated by ultracentrifugation. A proteomic analysis was performed to reveal the alternation of HDL protein composition and he antioxidant capacity of HDL was tested by low-density lipoprotein oxidation experiment. Furthermore, the activity or expression of HDL-associated enzymes were evaluated.

Key Findings: Inhalation of 4% H decreased the accumulation of OxPLs in rats. In vitro tests revealed that the different concentrations of H did not inhibit the formation of OxPLs mediated by non-enzymatic oxidation. H inhalation altered the components and enhanced the anti-oxidative capacity of HDL in rats fed with a high-fat diet. Further experiments showed that H significantly regulated the activity of lipoprotein-associated phospholipase A, paraoxonase-1, and the expression of lecithin:cholesterol acyltransferase.

Significance: Our findings revealed that H may reduce the OxPLs levels through its influence on HDL-associated enzymes that can act on OxPLs, suggesting that H can be used in alleviating diseases related to lipid peroxidation due to oxidative stress.