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

Biomed Pharmacother. 2021 Dec:144:112298. doi: 10.1016/j.biopha.2021.112298. Epub 2021 Oct 12.

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

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / therapeutic use*
  • Antifibrotic Agents / adverse effects
  • Antifibrotic Agents / therapeutic use*
  • Drug Development
  • Drug Discovery
  • Energy Metabolism / drug effects
  • Humans
  • Hypolipidemic Agents / adverse effects
  • Hypolipidemic Agents / therapeutic use*
  • Inflammation Mediators / metabolism
  • Lipid Metabolism / drug effects
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / pathology
  • Molecular Targeted Therapy
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Non-alcoholic Fatty Liver Disease / pathology
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction
  • Succinic Acid / metabolism*

Substances

  • Anti-Inflammatory Agents
  • Antifibrotic Agents
  • Hypolipidemic Agents
  • Inflammation Mediators
  • Receptors, G-Protein-Coupled
  • SUCNR1 protein, human
  • Succinic Acid