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This version published online on September 8, 2005
Endocrinology, doi:10.1210/en.2005-0237
A more recent version of this article appeared on December 1, 2005
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Submitted on February 25, 2005
Accepted on August 22, 2005

Peptide YY3-36 and glucagon-like peptide-17-36 inhibit food intake additively

Nicola M Neary, Caroline J Small, Maralyn R Druce, Adrian J Park, Sandra M Ellis, Nina M Semjonous, Catherine L Dakin, Karin Filipsson, Fang Wang, Aysha S Kent, Gary S Frost, Mohammad A Ghatei, and Stephen R Bloom*

Department of Metabolic Medicine, Hammersmith Hospital, Imperial College London, London W12 ONN, UK

* To whom correspondence should be addressed. E-mail: s.bloom{at}imperial.ac.uk.

Peptide YY (PYY) and glucagon like peptide-1 (GLP-1) are co-secreted from intestinal L-cells and plasma levels of both hormones rise after a meal. Peripheral administration of PYY3-36 and GLP-17-36 inhibit food intake when administered alone. However, their combined effects on appetite are unknown. We studied the effects of peripheral co-administration of PYY3-36 with GLP-17-36 in rodents and man. While high dose PYY3-36 (100 nmol/kg) and high dose GLP-17-36 (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 PYY3-36 (1 nmol/kg) and GLP-17-36 (10 nmol/kg), which alone had no effect on food intake, co-administration 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 following low-dose PYY3-36 or GLP-17-36 individually, but there were significantly more fos-positive neurons following co-administration. In contrast, there was no evidence of additive fos-stimulation in the brain stem. Finally, we co-administered PYY3-36 and GLP-17-36 in man. Ten lean fasted volunteers received 120 min infusions of saline, GLP-17-36(0.4pmol/kg/min), PYY3-36(0.4pmol/kg/min) and PYY3-36(0.4pmol/kg/min) + GLP-17-36(0.4pmol/kg/min) on four separate days. Energy intake from a buffet meal following combined PYY3-36 + GLP-17-36 treatment was reduced by 27% and was significantly lower than that following either treatment alone. Thus PYY3-36 and GLP-17-36, co-secreted after a meal, may inhibit food intake additively.




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