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

For a long time, hydrogen sulphide (H₂ S) was considered only as a toxic gas, inhibiting mitochondrial respiration at the level of cytochrome c oxidase, and an environmental pollutant. Nowadays, H₂ S 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).

This narrative review is based on literature search using PubMed.

From a bioenergetic perspective, H₂ S 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 H₂ S biosynthesis or exogenous compounds that release H₂ S, several studies demonstrated that H₂ S is a key player in liver glucose and lipid metabolism. Liver H₂ S content and biosynthesis were also altered in NAFLD animal models with the in vivo administration of H₂ S-releasing molecules preventing the further escalation into non-alcoholic-steatohepatitis. Liver steady-state levels of H₂ S, 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 H₂ S oxidation in liver dysfunction still remain scarce.

Since H₂ S emerges as a key regulator of liver metabolism and metabolic flexibility, further understanding the physiological relevance of mitochondrial H₂ S oxidation in liver energy homeostasis and its potential implication in chronic liver diseases are of great interest.