G protein-coupled receptors: Key molecules in metabolic associated fatty liver disease development

Nutr Res. 2021 Mar:87:70-79. doi: 10.1016/j.nutres.2020.12.019. Epub 2020 Dec 24.

Abstract

Metabolic associated fatty liver disease (MAFLD) is a range of hepatic disorders with progression to steatohepatitis with risk of development of fibrosis, cirrhosis, and hepatocellular carcinoma. MAFLD is strongly related to metabolic disorders of active fatty acids, which seem to be selective according to their specific ligand of G protein-coupled receptors (GPRs) located in immune response cells. An approach to study the pathophysiological mechanisms of MAFLD could be through the expression of active fatty acids ligands. The expression of GPRs is associated with obesity, microbiota environment, and dietary characteristics in patients with MAFLD. More specifically, GPR41, GPR43, GPR20, and GPR120 have been associated with alteration of lipid metabolism in hepatic and intestinal cells, and consequently they have a key role in metabolic diseases. We observed that GPR120 is not expressed in nonoverweight/obese patients, regardless of the presence of MAFLD; meanwhile the expression of GPR41 is increased in patients with lean MAFLD. GPRs role in liver disease is intriguing and a field of research opportunity. More studies are necessary to define the role of active fatty acids in the development of metabolic diseases.

Keywords: Free fatty acids; Lipid metabolism; Microbiota; Obesity.

Publication types

  • Review

MeSH terms

  • Animals
  • Body Weight
  • Fatty Acids / metabolism
  • Gastrointestinal Microbiome
  • Hepatocytes / metabolism
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Lipid Metabolism
  • Non-alcoholic Fatty Liver Disease / complications
  • Non-alcoholic Fatty Liver Disease / metabolism*
  • Obesity / complications
  • Obesity / metabolism
  • Receptors, G-Protein-Coupled / metabolism*

Substances

  • Fatty Acids
  • Receptors, G-Protein-Coupled