Blockade of central GLP-1 receptors prevents CART-induced hypophagia and brain c-Fos expression.
Central administration of both CART and GLP-1 reduces feeding and increases c-Fos in brain areas associated with food intake. To determine whether aspects of CART's effects were mediated through GLP-1's action, we examined whether the GLP-1 receptor antagonist des-His1-Glu9-exendin-4 (EX) blocked CART-induced feeding inhibition, and c-Fos activation. An i.c.v. dose of 100 microg EX blocked the feeding inhibitory action of 1 microg of CART i.c.v. and prevented CART-induced c-Fos expression at multiple hindbrain and hypothalamic sites. These data suggest that i.c.v. CART administration activates a central release of GLP-1 to inhibit feeding and produce widespread neural activation.
Aja
Susan
S
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 618, Baltimore, MD 21205, USA. saja1@jhmi.edu
Ewing
Cassandra
C
Lin
Jennifer
J
Hyun
Jayson
J
Moran
Timothy H
TH
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D000077270:Exenatide; D005247:Feeding Behavior / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage* / Q000378:metabolism; D000067757:Glucagon-Like Peptide-1 Receptor; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D008297:Male; D009419:Nerve Tissue Proteins / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D018377:Neurotransmitter Agents / Q000008:administration & dosage; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000378:metabolism; D010455:Peptides / Q000008:administration & dosage; D016760:Proto-Oncogene Proteins c-fos / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012844:Sincalide / Q000494:pharmacology; D014688:Venoms / Q000008:administration & dosage; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D010455:Peptides; D016760:Proto-Oncogene Proteins c-fos; D018027:Receptors, Glucagon; D014688:Venoms; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; C428723:cocaine- and amphetamine-regulated transcript protein (55-102); C055453:glucagon-like peptide 1 (7-36)amide; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; D012844:Sincalide