Foresight regarding drug candidates acting on the succinate–GPR91 signalling pathway for non-alcoholic steatohepatitis (NASH) treatment

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and it is a liver manifestation of metabolic syndrome, with a histological spectrum from simple steatosis to non-alcoholic steatohepatitis (NASH). NASH can evolve into progressive liver fibrosis and eventually lead to liver cirrhosis. The pathological mechanism of NASH is multifactorial, involving a series of metabolic disorders and changes that trigger low-level inflammation in the liver and other organs. In the pathogenesis of NASH, the signal transduction pathway involving succinate and the succinate receptor (G-protein-coupled receptor 91, GPR91) regulates inflammatory cell activation and liver fibrosis. This review describes the mechanism of the succinate–GPR91 signalling pathway in NASH and summarizes the drugs that act on this pathway, with the aim of providing a new approach to NASH treatment.

Keywords

• Non-alcoholic steatohepatitis (NASH)
• Non-alcoholic fatty liver disease (NAFLD)
• Succinate–GPR91
• Liver fibrosis
• Hepatic stellate cells (HSCs)