This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Neary, N. M. Articles by Bloom, S. R. Search for Related Content PubMed PubMed Citation Articles by Neary, N. M. Articles by Bloom, S. R.

Peptide YY_3–36 and Glucagon-Like Peptide-1_7–36 Inhibit Food Intake Additively

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

Address all correspondence and requests for reprints to: Professor S. R. Bloom, Department of Metabolic Medicine, Hammersmith Hospital, Imperial College London, 6th Floor, Commonwealth Building, Du Cane Road, London W12 ONN, United Kingdom. E-mail: s.bloom{at}imperial.ac.uk.

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.

This article has been cited by other articles:

				D. A. Van Vugt Brain imaging studies of appetite in the context of obesity and the menstrual cycle Hum. Reprod. Update, November 19, 2009; (2009) dmp051v1. [Abstract] [Full Text] [PDF]

				T. H. Moran and M. J. Dailey Gut Peptides: Targets for Antiobesity Drug Development? Endocrinology, June 1, 2009; 150(6): 2526 - 2530. [Abstract] [Full Text] [PDF]

				E. Karra, K. Chandarana, and R. L. Batterham The role of peptide YY in appetite regulation and obesity J. Physiol., January 1, 2009; 587(1): 19 - 25. [Abstract] [Full Text] [PDF]

				A. Geliebter, C. N. Ochner, and R. Aviram-Friedman Appetite-Related Gut Peptides in Obesity and Binge Eating Disorder American Journal of Lifestyle Medicine, July 1, 2008; 2(4): 305 - 314. [Abstract] [PDF]

				S. R. Bloom, F. P. Kuhajda, I. Laher, X. Pi-Sunyer, G. V. Ronnett, T. M.M. Tan, and D. S. Weigle The Obesity Epidemic: Pharmacological Challenges Mol. Interv., April 1, 2008; 8(2): 82 - 98. [Abstract] [Full Text] [PDF]

				O. B. Chaudhri, K. Wynne, and S. R. Bloom Can Gut Hormones Control Appetite and Prevent Obesity? Diabetes Care, February 1, 2008; 31(Supplement_2): S284 - S289. [Abstract] [Full Text] [PDF]

				J. D. Roth, T. Coffey, C. M. Jodka, H. Maier, J. R. Athanacio, C. M. Mack, C. Weyer, and D. G. Parkes Combination Therapy with Amylin and Peptide YY[3 36] in Obese Rodents: Anorexigenic Synergy and Weight Loss Additivity Endocrinology, December 1, 2007; 148(12): 6054 - 6061. [Abstract] [Full Text] [PDF]

				Y.-T. Kuo, J. R. C. Parkinson, O. B. Chaudhri, A. H. Herlihy, P.-W. So, W. S. Dhillo, C. J. Small, S. R. Bloom, and J. D. Bell The Temporal Sequence of Gut Peptide CNS Interactions Tracked In Vivo by Magnetic Resonance Imaging J. Neurosci., November 7, 2007; 27(45): 12341 - 12348. [Abstract] [Full Text] [PDF]

				A. A. Ortiz, L. F. Milardo, L. B. DeCarr, T. M. Buckholz, M. R. Mays, T. H. Claus, J. N. Livingston, C. D. Mahle, and K. J. Lumb A Novel Long-Acting Selective Neuropeptide Y2 Receptor Polyethylene Glycol-Conjugated Peptide Agonist Reduces Food Intake and Body Weight and Improves Glucose Metabolism in Rodents J. Pharmacol. Exp. Ther., November 1, 2007; 323(2): 692 - 700. [Abstract] [Full Text] [PDF]

				K. L. Whited, P. Tso, and H. E. Raybould Involvement of Apolipoprotein A-IV and Cholecystokinin1 Receptors in Exogenous Peptide YY3 36-Induced Stimulation of Intestinal Feedback Endocrinology, October 1, 2007; 148(10): 4695 - 4703. [Abstract] [Full Text] [PDF]

				B. Sloth, L. Davidsen, J. J. Holst, A. Flint, and A. Astrup Effect of subcutaneous injections of PYY1-36 and PYY3-36 on appetite, ad libitum energy intake, and plasma free fatty acid concentration in obese males Am J Physiol Endocrinol Metab, August 1, 2007; 293(2): E604 - E609. [Abstract] [Full Text] [PDF]

				C. Martins, L. M Morgan, S. R Bloom, and M D. Robertson Effects of exercise on gut peptides, energy intake and appetite J. Endocrinol., May 1, 2007; 193(2): 251 - 258. [Abstract] [Full Text] [PDF]

				B. Sloth, J. J. Holst, A. Flint, N. T. Gregersen, and A. Astrup Effects of PYY1-36 and PYY3-36 on appetite, energy intake, energy expenditure, glucose and fat metabolism in obese and lean subjects Am J Physiol Endocrinol Metab, April 1, 2007; 292(4): E1062 - E1068. [Abstract] [Full Text] [PDF]

				B. M. McGowan, S. A. Stanley, N. E. White, A. Spangeus, M. Patterson, E. L. Thompson, K. L. Smith, J. Donovan, J. V. Gardiner, M. A. Ghatei, et al. Hypothalamic mapping of orexigenic action and Fos-like immunoreactivity following relaxin-3 administration in male Wistar rats Am J Physiol Endocrinol Metab, March 1, 2007; 292(3): E913 - E919. [Abstract] [Full Text] [PDF]

				R. Arumugam, D. Fleenor, and M. Freemark Lactogenic and Somatogenic Hormones Regulate the Expression of Neuropeptide Y and Cocaine- and Amphetamine-Regulated Transcript in Rat Insulinoma (INS-1) Cells: Interactions with Glucose and Glucocorticoids Endocrinology, January 1, 2007; 148(1): 258 - 267. [Abstract] [Full Text] [PDF]

				K. G. Murphy, W. S. Dhillo, and S. R. Bloom Gut Peptides in the Regulation of Food Intake and Energy Homeostasis Endocr. Rev., December 1, 2006; 27(7): 719 - 727. [Abstract] [Full Text] [PDF]

				N. Rozengurt, S. V. Wu, M. C. Chen, C. Huang, C. Sternini, and E. Rozengurt Colocalization of the {alpha}-subunit of gustducin with PYY and GLP-1 in L cells of human colon Am J Physiol Gastrointest Liver Physiol, November 1, 2006; 291(5): G792 - G802. [Abstract] [Full Text] [PDF]

				E. Rozengurt Taste Receptors in the Gastrointestinal Tract. I. Bitter taste receptors and {alpha}-gustducin in the mammalian gut Am J Physiol Gastrointest Liver Physiol, August 1, 2006; 291(2): G171 - G177. [Abstract] [Full Text] [PDF]

				A. A. Young Obesity: A Peptide YY-Deficient, But Not Peptide YY- Resistant, State Endocrinology, January 1, 2006; 147(1): 1 - 2. [Full Text] [PDF]