Exendin-4 potently decreases ghrelin levels in fasting rats.
Ghrelin is a potent orexigenic and adipogenic hormone that strongly influences fat deposition and the generation of hunger in obesity. Indeed, hyperghrelinemia appears to promote an increase in food intake as seen in Prader-Willi Syndrome (PWS). Exendin (Ex)-4 is an agonist of the glucagon-like peptide (GLP)-1 receptor (GLP-1r) that has anorexigenic and fat-reducing properties. Here, we report that Ex-4 reduces the levels of ghrelin by up to 74% in fasted rats. These effects are dose dependent and long lasting (up to 8 h), and they can be detected after both central and peripheral administration of Ex-4. Suppression of ghrelin was neither mimicked by GLP-1(7-36)-NH(2) nor blocked by the GLP-1r antagonist Ex-(9-39). Moreover, it was independent of the levels of leptin and insulin. The decrease in ghrelin levels induced by Ex-4 may explain the reduced food intake in fasted rats, justifying the more potent anorexigenic effects of Ex-4 when compared with GLP-1. As well as the potential benefits of Ex-4 in type 2 diabetes, the potent effects of Ex-4 on ghrelin make it tempting to speculate that Ex-4 could offer a therapeutic option for PWS and other syndromes characterized by substantial amounts of circulating ghrelin.
Pérez-Tilve
Diego
D
Department of Functional Biology and Health Sciences, Faculty of Biology, Laboratory of Endocrinology, Campus of Vigo, As Lagoas-Marcosende, University of Vigo, E-36310 Vigo, Spain.
González-Matías
Lucas
L
Alvarez-Crespo
Mayte
M
Leiras
Roberto
R
Tovar
Sulay
S
Diéguez
Carlos
C
Mallo
Federico
F
D000818:Animals; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology; D000077270:Exenatide; D005215:Fasting; D054439:Ghrelin; D006801:Humans; D007276:Injections, Intraventricular; D007700:Kinetics; D008297:Male; D036361:Peptide Hormones / Q000097:blood* / Q000187:drug effects; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D011218:Prader-Willi Syndrome / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014688:Venoms / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D054439:Ghrelin; D036361:Peptide Hormones; D010455:Peptides; D014688:Venoms; D000077270:Exenatide