Peptide YY3-36 and glucagon-like peptide-17-36 inhibit food intake additively.
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.
Neary
Nicola M
NM
Department of Metabolic Medicine, Hammersmith Hospital, Imperial College London, UK.
Small
Caroline J
CJ
Druce
Maralyn R
MR
Park
Adrian J
AJ
Ellis
Sandra M
SM
Semjonous
Nina M
NM
Dakin
Catherine L
CL
Filipsson
Karin
K
Wang
Fang
F
Kent
Aysha S
AS
Frost
Gary S
GS
Ghatei
Mohammad A
MA
Bloom
Stephen R
SR
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
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