title: Possible involvement of melanocortin-4-receptor and AMP-activated protein kinase in the interaction of glucagon-like peptide-1 and leptin on feeding in rats.
abstract: Glucagon-like peptide-1 (GLP-1) and leptin are anorectic hormones produced in the small intestine and white adipose tissue, respectively. Investigating how these hormones act together as an integrated anorectic signal is important to elucidate a mechanism to maintain energy balance. In the present study, coadministration of subthreshold GLP-1 and leptin dramatically reduced feeding in rats. Although coadministration of GLP-1 with leptin did not enhance leptin signal transduction in the hypothalamus, it significantly decreased phosphorylation of AMP-activated protein kinase (AMPK). In addition, coadministration of GLP-1 with leptin significantly increased proopiomelanocortin (POMC) mRNA levels. Considering that α-melanocortin stimulating hormone (α-MSH) is derived from POMC and functions through the melanocortin-4-receptor (MC4-R) as a key molecule involved in feeding reduction, the interaction of GLP-1 and leptin on feeding reduction may be mediated through the α-MSH/MC4-R system. As expected, the interaction of GLP-1 and leptin was abolished by intracerebroventricular preadministration of the MC4-R antagonists agouti-related peptide and SHU9119. Taken together, GLP-1 and leptin cooperatively reduce feeding at least in part via inhibition of AMPK following binding of α-MSH to MC4-R.
authors.affiliation: Frontier Science Research Center, University of Miyazaki, Miyazaki 889-1692, Japan.
authors.forename: Paul-Emile
authors.initials: PE
authors.lastname: Poleni
authors.forename: Sayaka
authors.initials: S
authors.lastname: Akieda-Asai
authors.forename: Shuichi
authors.initials: S
authors.lastname: Koda
authors.forename: Maya
authors.initials: M
authors.lastname: Sakurai
authors.forename: Cho-Rong
authors.initials: CR
authors.lastname: Bae
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Senba
authors.forename: Youn-Soo
authors.initials: YS
authors.lastname: Cha
authors.forename: Mayumi
authors.initials: M
authors.lastname: Furuya
authors.forename: Yukari
authors.initials: Y
authors.lastname: Date
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects*; D005247:Feeding Behavior / Q000187:drug effects*; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage*; D020738:Leptin / Q000008:administration & dosage*; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044105:Receptor, Melanocortin, Type 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000521:alpha-MSH / Q000378:metabolism
chemical_list: D020738:Leptin; D044105:Receptor, Melanocortin, Type 4; C103272:SHU 9119; D000521:alpha-MSH; D052216:Glucagon-Like Peptide 1; D009074:Melanocyte-Stimulating Hormones; D055372:AMP-Activated Protein Kinases