Effects of AM80 compared to AC261066 in a high fat diet mouse model of liver disease. Academic Article uri icon

Overview

abstract

  • The roles of retinoids in nonalcoholic fatty liver disease (NAFLD) remain unclear and a better understanding may lead to therapies that prevent or limit NAFLD progression. We examined the actions of retinoic acid receptor (RAR) agonists- AM80 for RARα and AC261066 for RARβ2- in a murine model of NAFLD. We fed wild type C57Bl/6 mice a chow or a 45% high fat diet (HFD) for 12 weeks, followed by 4 additional weeks with the HFD+AM80; HFD+AC261066; or HFD. The HFD+AM80 group showed greater hyperglycemia and glucose intolerance compared to other groups. Histopathological evaluation of the livers showed the highest degree of steatosis, triglycerides levels, and inflammation, assessed by F4/80 staining, in the HFD+AM80-treated compared to the HFD, the HFD+AC261066, and chow-fed mice. Liver vitamin A (retinol (ROL)) and retinyl palmitate levels were markedly lower in all HFD groups compared to chow-fed controls. HFD+AC261066-treated mice showed higher levels of a key intracellular ROL transporter, retinol-binding protein-1 (RBP1) compared to the HFD and HFD+AM80 groups. In conclusion, these data demonstrate that the selective RARα agonist AM80 exacerbates HFD-induced NAFLD and hyperglycemia. These findings should inform future studies examining the therapeutic potential of RAR agonists in HFD-related disorders.

publication date

  • January 24, 2019

Research

keywords

  • Benzoates
  • Dietary Fats
  • Liver
  • Non-alcoholic Fatty Liver Disease
  • Tetrahydronaphthalenes
  • Thiazoles

Identity

PubMed Central ID

  • PMC6345457

Scopus Document Identifier

  • 85060446937

Digital Object Identifier (DOI)

  • 10.1002/hep.25798

PubMed ID

  • 30677086

Additional Document Info

volume

  • 14

issue

  • 1