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

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.