title: Central GLP-1 receptor activation improves cholesterol metabolism partially independent of its effect on food intake.
abstract: 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 LDLR and CYP7A1 was increased after the repeated dose treatment, and there was no change in HMG CoA reductase. These changes were blocked by co-treatment of exendin-9, and not replicated by pair feeding to the significant extent. Central GLP-1 receptor activation showed profound effects on peripheral lipid metabolism, which were partially independent of its effect on food intake.
authors.affiliation: a Department of Pharmacology & Toxicology, Zydus Research Centre, Cadila Healthcare Limited, Sarkhej-Bavla N.H.No.8A, Moraiya, Ahmedabad 382210, India.|c K.B. Institute of Pharmaceutical Education and Research, Gandhinagar 382023, Gujarat.
authors.forename: Vishal
authors.initials: V
authors.lastname: Patel
authors.affiliation: a Department of Pharmacology & Toxicology, Zydus Research Centre, Cadila Healthcare Limited, Sarkhej-Bavla N.H.No.8A, Moraiya, Ahmedabad 382210, India.
authors.forename: Amit Arvind
authors.initials: AA
authors.lastname: Joharapurkar
authors.affiliation: a Department of Pharmacology & Toxicology, Zydus Research Centre, Cadila Healthcare Limited, Sarkhej-Bavla N.H.No.8A, Moraiya, Ahmedabad 382210, India.
authors.forename: Samadhan Govind
authors.initials: SG
authors.lastname: Kshirsagar
authors.affiliation: a Department of Pharmacology & Toxicology, Zydus Research Centre, Cadila Healthcare Limited, Sarkhej-Bavla N.H.No.8A, Moraiya, Ahmedabad 382210, India.
authors.forename: Kartikkumar Navinchandra
authors.initials: KN
authors.lastname: Patel
authors.affiliation: b Department of Medicinal Chemistry, Zydus Research Centre, Cadila Healthcare Limited, Sarkhej-Bavla N.H.No.8A, Moraiya, Ahmedabad 382210, India.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Bahekar
authors.affiliation: c K.B. Institute of Pharmaceutical Education and Research, Gandhinagar 382023, Gujarat.
authors.forename: Gaurang
authors.initials: G
authors.lastname: Shah
authors.affiliation: a Department of Pharmacology & Toxicology, Zydus Research Centre, Cadila Healthcare Limited, Sarkhej-Bavla N.H.No.8A, Moraiya, Ahmedabad 382210, India.
authors.forename: Mukul R
authors.initials: MR
authors.lastname: Jain
keywords: exendin-4; exendine-4; hamsters; hypercholesterolemia; hypercholestérolémie; intracerebroventricular; intracérébroventriculaire; tyloxapol