Effect of feeding a high fat diet on hydrogen sulfide (H2S) metabolism in the mouse

•H2S biosynthesis is impaired in tissues from high fat fed mice.•Expression of cystathionine γ lyase is reduced in tissues from high fat fed mice.•H2S deficiency precedes development of atherosclerosis in high fat fed mice. Hydrogen sulfide (H2S) has complex effects in inflammation with both pro- and anti-inflammatory actions of this gas reported. Recent work suggests that a deficiency of H2S occurs in, and may contribute to, the chronic inflammation which underpins ongoing atherosclerotic disease. However, whether a high fat diet, predisposing to atherosclerosis, affects H2S metabolism is not known. In this study we assessed H2S metabolism in different tissues of mice fed a high fat diet for up to 16weeks. Ex vivo biosynthesis of H2S was reduced in liver, kidney and lung of high fat fed mice. Western blotting revealed deficiency of cystathionine γ lyase (CSE) in liver and lung with increased expression of cystathionine β synthetase (CBS) in liver and kidney. Expression of 3-mercaptopyruvate sulfurtransferase (3-MST) was reduced in liver but not other tissues. Aortic endothelial cell CSE was also reduced in high fat fed animals as determined immunohistochemically. Plasma H2S concentration was not changed in these animals. No evidence of lipid deposition was apparent in aortae from high fat fed animals and plasma serum amyloid A (SAA) and C-reactive protein (CRP) were also unchanged suggesting lack of frank atherosclerotic disease. Plasma IL-6, IL12p40 and G-CSF levels were increased by high fat feeding whilst other cytokines including IL-1α, IL-1b and TNF-α were not altered. These results suggest that deficiency of tissue CSE and H2S occurs in mice fed a high fat diet and that this change takes place prior to development of frank atherosclerotic disease.