Hydrogen sulphide in liver glucose/lipid metabolism and non-alcoholic fatty liver disease

Background For a long time, hydrogen sulphide (H2S) was considered only as a toxic gas, inhibiting mitochondrial respiration at the level of cytochrome c oxidase, and an environmental pollutant. Nowadays, H2S is recognized as the third mammalian gasotransmitter, playing an important role in inflammation, septic shock, ischaemia reperfusion events, cardiovascular disease and more recently in liver physiology and chronic liver diseases such as non-alcoholic fatty liver disease (NAFLD). Methods This narrative review is based on literature search using PubMed. Results From a bioenergetic perspective, H2S is a very unique molecule, serving as a mitochondrial poison at high concentrations or as an inorganic mitochondrial substrate at low concentrations. By using transgenic animal models to specifically modulate liver H2S biosynthesis or exogenous compounds that release H2S, several studies demonstrated that H2S is a key player in liver glucose and lipid metabolism. Liver H2S content and biosynthesis were also altered in NAFLD animal models with the in vivo administration of H2S-releasing molecules preventing the further escalation into non-alcoholic-steatohepatitis. Liver steady-state levels of H2S, and hence its cell signalling properties, are controlled by a tight balance between its biosynthesis, mainly through the transsulphuration pathway, and its mitochondrial oxidation via the sulphide oxidizing unit. However, studies investigating mitochondrial H2S oxidation in liver dysfunction still remain scarce. Conclusions Since H2S emerges as a key regulator of liver metabolism and metabolic flexibility, further understanding the physiological relevance of mitochondrial H2S oxidation in liver energy homeostasis and its potential implication in chronic liver diseases are of great interest.

Automated summary

Hydrogen sulphide (H2S) was previously seen as a toxic gas and environmental pollutant, but is now recognized as the third mammalian gasotransmitter with key roles in inflammation and diseases. In the liver, H2S plays a crucial role in glucose and lipid metabolism and may have implications in chronic liver diseases. Further research is needed to understand the physiological relevance of mitochondrial H2S oxidation and its impact on liver energy homeostasis.