Exendin-4, a glucagon-like peptide-1 receptor agonist downregulates hepatic receptor for advanced glycation end products in non-alcoholic steatohepatitis rat model

Arch Physiol Biochem. 2018 Feb;124(1):10-17. doi: 10.1080/13813455.2017.1348362. Epub 2017 Jul 11.

Abstract

Context: Exendin-4, a glucagon-like peptide-1 receptor agonist has been shown to have curative effects on hepatic steatosis in murine models.

Objective: The present study aimed to elucidate the effect of Exendin-4 on hepatic receptor for advanced glycation end products (RAGE) mRNA expression in non-alcoholic steatohepatitis (NASH) rat model induced by high-fat diet.

Methods: NASH was induced by high-fat diet intake, and Exendin-4 was given in two different doses. After 12 weeks, liver enzyme levels, hepatic triglycerides, antioxidant enzymes and malondialdehyde (MDA) levels, and mRNA RAGE was detected using RT-PCR.

Results: Exendin-4 in high dose reduced significantly liver enzymes activity, hepatic triglycerides, MDA levels and hepatic mRNA RAGE expression levels with significantly higher antioxidant enzymes activity.

Conclusions: Our results give further insights into the mechanisms underlying the curative role of Exendin-4 in NASH, suggesting that interference with RAGE may be a useful therapeutic approach to NASH.

Keywords: Exendin-4; high-fat diet; hormone; non-alcoholic steatohepatitis; obesity; oxidative stress; receptor for advanced glycation end products.

MeSH terms

  • Animals
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Diet, High-Fat / adverse effects
  • Disease Models, Animal*
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects*
  • Enzyme Induction / drug effects
  • Exenatide
  • Glucagon-Like Peptide-1 Receptor / agonists
  • Glucagon-Like Peptide-1 Receptor / metabolism
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / therapeutic use*
  • Insulin Resistance
  • Lipid Peroxidation / drug effects
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / etiology
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Non-alcoholic Fatty Liver Disease / pathology
  • Organ Size / drug effects
  • Oxidative Stress / drug effects
  • Oxidoreductases / chemistry
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism
  • Peptides / administration & dosage
  • Peptides / therapeutic use*
  • Random Allocation
  • Rats, Wistar
  • Receptor for Advanced Glycation End Products / antagonists & inhibitors*
  • Receptor for Advanced Glycation End Products / genetics
  • Receptor for Advanced Glycation End Products / metabolism
  • Triglycerides / metabolism
  • Venoms / administration & dosage
  • Venoms / therapeutic use*

Substances

  • Ager protein, rat
  • Biomarkers
  • Glp1r protein, rat
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Peptides
  • Receptor for Advanced Glycation End Products
  • Triglycerides
  • Venoms
  • Exenatide
  • Oxidoreductases