title: Peptide YY3-36 and glucagon-like peptide-17-36 inhibit food intake additively.
abstract: Peptide YY (PYY) and glucagon like peptide (GLP)-1 are cosecreted from intestinal L cells, and plasma levels of both hormones rise after a meal. Peripheral administration of PYY(3-36) and GLP-1(7-36) inhibit food intake when administered alone. However, their combined effects on appetite are unknown. We studied the effects of peripheral coadministration of PYY(3-36) with GLP-1(7-36) in rodents and man. Whereas high-dose PYY(3-36) (100 nmol/kg) and high-dose GLP-1(7-36) (100 nmol/kg) inhibited feeding individually, their combination led to significantly greater feeding inhibition. Additive inhibition of feeding was also observed in the genetic obese models, ob/ob and db/db mice. At low doses of PYY(3-36) (1 nmol/kg) and GLP-1(7-36) (10 nmol/kg), which alone had no effect on food intake, coadministration led to significant reduction in food intake. To investigate potential mechanisms, c-fos immunoreactivity was quantified in the hypothalamus and brain stem. In the hypothalamic arcuate nucleus, no changes were observed after low-dose PYY(3-36) or GLP-1(7-36) individually, but there were significantly more fos-positive neurons after coadministration. In contrast, there was no evidence of additive fos-stimulation in the brain stem. Finally, we coadministered PYY(3-36) and GLP-1(7-36) in man. Ten lean fasted volunteers received 120-min infusions of saline, GLP-1(7-36) (0.4 pmol/kg.min), PYY(3-36) (0.4 pmol/kg.min), and PYY(3-36) (0.4 pmol/kg.min) + GLP-1(7-36) (0.4 pmol/kg.min) on four separate days. Energy intake from a buffet meal after combined PYY(3-36) + GLP-1(7-36) treatment was reduced by 27% and was significantly lower than that after either treatment alone. Thus, PYY(3-36) and GLP-1(7-36), cosecreted after a meal, may inhibit food intake additively.
authors.affiliation: Department of Metabolic Medicine, Hammersmith Hospital, Imperial College London, UK.
authors.forename: Nicola M
authors.initials: NM
authors.lastname: Neary
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Small
authors.forename: Maralyn R
authors.initials: MR
authors.lastname: Druce
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Park
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Ellis
authors.forename: Nina M
authors.initials: NM
authors.lastname: Semjonous
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Dakin
authors.forename: Karin
authors.initials: K
authors.lastname: Filipsson
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Aysha S
authors.initials: AS
authors.lastname: Kent
authors.forename: Gary S
authors.initials: GS
authors.lastname: Frost
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Ghatei
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Bloom
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003920:Diabetes Mellitus / Q000235:genetics / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D004357:Drug Synergism; D004435:Eating / Q000187:drug effects*; D002149:Energy Intake / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D005934:Glucagon / Q000008:administration & dosage / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009765:Obesity / Q000235:genetics / Q000503:physiopathology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D019894:Peptide YY / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats
chemical_list: D004338:Drug Combinations; D010446:Peptide Fragments; D019894:Peptide YY; C061970:glucagon-like peptide 1 (7-36); C061785:peptide YY (3-36); D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon