Modulation of aryl hydrocarbon receptor (AHR) and the NAD +-consuming enzyme CD38: Searches of therapeutic options for nonalcoholic fatty liver disease (NAFLD)

Biochem Pharmacol. 2020 May;175:113905. doi: 10.1016/j.bcp.2020.113905. Epub 2020 Mar 10.

Abstract

The aryl hydrocarbon receptor (AHR) has been characterized as multifunctional, ligand-activated transcription factor. Recently, evidence has been obtained that AHR is involved in NAD+ and energy homeostasis in cooperation with NAD+-consuming enzymes including CD38, TiPARP and sirtuins. AHR and CD38 may adversely or beneficially modulate nonalcoholic fatty liver disease (NAFLD) which is associated with obesity, a worldwide major health problem. Although nutritional status and lifestyle are the major factors involved in the prevalence of obesity and NAFLD, modulation of AHR and CD38 has been demonstrated to provide therapeutic options. For example, inhibition of hepatic CD38 and activation of AHR, e.g., by dietary flavonoids may beneficially affect NAFLD. In addition, NAFLD-associated decrease of NAD+ may be restored by administration of the NAD+ precursor nicotinamide riboside.

Keywords: 2378-Tetrachlorodibenzo-p-dioxin = TCDD (PubChem CID 15625); Aryl hydrocarbon receptor; CD38; Indigo (PubChem CID 10215); Nicotinamide riboside; Nicotinamide riboside (PubChem CID 439924); Nonalcoholic fatty liver disease; Quercetin; Quercetin (PubChem CID 5280343).

Publication types

  • Review

MeSH terms

  • ADP-ribosyl Cyclase 1 / genetics
  • ADP-ribosyl Cyclase 1 / metabolism*
  • Adipocytes / metabolism
  • Adipocytes / pathology
  • Animals
  • Humans
  • Liver / metabolism
  • Liver / pathology
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • NAD / genetics
  • NAD / metabolism*
  • Non-alcoholic Fatty Liver Disease / genetics
  • Non-alcoholic Fatty Liver Disease / metabolism*
  • Non-alcoholic Fatty Liver Disease / pathology*
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism*

Substances

  • Membrane Glycoproteins
  • Receptors, Aryl Hydrocarbon
  • NAD
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1