title: The contribution of serotonin 5-HT2C and melanocortin-4 receptors to the satiety signaling of glucagon-like peptide 1 and liraglutide, a glucagon-like peptide 1 receptor agonist, in mice.
abstract: Glucagon-like peptide 1 (GLP-1), an insulinotropic gastrointestinal peptide produced mainly from intestinal endocrine L-cells, and liraglutide, a GLP-1 receptor (GLP-1R) agonist, induce satiety. The serotonin 5-HT2C receptor (5-HT2CR) and melanoroctin-4 receptor (MC4R) are involved in the regulation of food intake. Here we show that systemic administration of GLP-1 (50 and 200μg/kg)-induced anorexia was blunted in mice with a 5HT2CR null mutation, and was attenuated in mice with a heterozygous MC4R mutation. On the other hand, systemic administration of liraglutide (50 and 100μg/kg) suppressed food intake in mice lacking 5-HT2CR, mice with a heterozygous mutation of MC4R and wild-type mice matched for age. Moreover, once-daily consecutive intraperitoneal administration of liraglutide (100μg/kg) over 3days significantly suppressed daily food intake and body weight in mice with a heterozygous mutation of MC4R as well as wild-type mice. These findings suggest that GLP-1 and liraglutide induce anorexia via different central pathways.
authors.affiliation: Department of Lifestyle Medicine, Biomedical Engineering Center, Tohoku University, Japan. katsu@trc.med.tohoku.ac.jp
authors.forename: Katsunori
authors.initials: K
authors.lastname: Nonogaki
authors.forename: Marina
authors.initials: M
authors.lastname: Suzuki
authors.forename: Marin
authors.initials: M
authors.lastname: Sanuki
authors.forename: Mamoru
authors.initials: M
authors.lastname: Wakameda
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Tamari
mesh_terms: D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D000067757:Glucagon-Like Peptide-1 Receptor; D006579:Heterozygote; D000069450:Liraglutide; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics / Q000502:physiology*; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics / Q000502:physiology*; D018027:Receptors, Glucagon / Q000819:agonists*; D012528:Satiety Response / Q000187:drug effects*; D015398:Signal Transduction
chemical_list: C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D044105:Receptor, Melanocortin, Type 4; D044405:Receptor, Serotonin, 5-HT2C; D018027:Receptors, Glucagon; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1