Central GLP-1 receptor activation improves cholesterol metabolism partially independent of its effect on food intake

Glucagon-like peptide-1 (GLP-1) receptor agonists modulate lipid metabolism, apart from controlling glucose homeostasis. We investigated the role of central GLP-1 receptor (GLP-1R) agonism in regulation of hepatic lipid metabolism in cholesterol-fed hamsters. Cholesterol-fed hamsters were treated by intracerebroventricular (i.c.v.) route with exendin-4, as acute or repeated dose regimen and compared with hamsters pair-fed to the exendin-treated hamsters and with hamsters co-treated with GLP-1 antagonist exendin-9. Effect of acute treatment was observed on food intake, tyloxapol-induced hypertriglyceridemia, and corn oil induced post prandial lipemia. Plasma and hepatic lipids and changes in the expression of hepatic genes involved in lipid metabolism were assessed after chronic administration. Acute, as well as repeated dose, treatment of exendin-4 showed significant changes in hepatic lipids, circulating fatty acids, triglycerides, LDL, and cholesterol. Expression of SREBP-1c was reduced while that of LD...