Inhibition of Food Intake in Obese Subjects by Peptide YY3-36

doi:10.1056/NEJMoa030204

Volume 349:941-948		September 4, 2003		Number 10

Inhibition of Food Intake in Obese Subjects by Peptide YY_3–36

Rachel L. Batterham, M.B., B.S., Mark A. Cohen, M.B., Ch.B., Sandra M. Ellis, B.Sc., Carel W. Le Roux, M.B., Ch.B., Dominic J. Withers, M.B., B.S., Ph.D., Gary S. Frost, Ph.D., Mohammad A. Ghatei, Ph.D., and Stephen R. Bloom, M.D., D.Sc.

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ABSTRACT

Background The gut hormone fragment peptide YY_3–36 (PYY)reduces appetite and food intake when infused into subjectsof normal weight. In common with the adipocyte hormone leptin,PYY reduces food intake by modulating appetite circuits in thehypothalamus. However, in obesity there is a marked resistanceto the action of leptin, which greatly limits its therapeuticeffectiveness. We investigated whether obese subjects were alsoresistant to the anorectic effects of PYY.

Methods We compared the effects of PYY infusion on appetiteand food intake in 12 obese and 12 lean subjects in a double-blind,placebo-controlled, crossover study. The plasma levels of PYY,ghrelin, leptin, and insulin were also determined.

Results Caloric intake during a buffet lunch offered two hoursafter the infusion of PYY was decreased by 30 percent in theobese subjects (P<0.001) and 31 percent in the lean subjects(P<0.001). PYY infusion also caused a significant decreasein the cumulative 24-hour caloric intake in both obese and leansubjects. PYY infusion reduced plasma levels of the appetite-stimulatoryhormone ghrelin. Endogenous fasting and postprandial levelsof PYY were significantly lower in obese subjects (the mean[±SE] fasting PYY levels were 10.2±0.7 pmol perliter in the obese group and 16.9±0.8 pmol per literin the lean group, P<0.001). Furthermore, the fasting PYYlevels correlated negatively with the body-mass index (r = –0.84,P<0.001).

Conclusions We found that obese subjects were not resistantto the anorectic effects of PYY. Endogenous PYY levels werelow in the obese subjects, suggesting that PYY deficiency maycontribute to the pathogenesis of obesity.

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From the Department of Metabolic Medicine, Imperial College Faculty of Medicine at Hammersmith Campus, Du Cane Rd., London W12 0NN, United Kingdom.

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Neary, N. M., Small, C. J., Druce, M. R., Park, A. J., Ellis, S. M., Semjonous, N. M., Dakin, C. L., Filipsson, K., Wang, F., Kent, A. S., Frost, G. S., Ghatei, M. A., Bloom, S. R. (2005). Peptide YY3-36 and Glucagon-Like Peptide-17-36 Inhibit Food Intake Additively. Endocrinology 146: 5120-5127 [Abstract] [Full Text]
Feinle-Bisset, C., Patterson, M., Ghatei, M. A., Bloom, S. R., Horowitz, M. (2005). Fat digestion is required for suppression of ghrelin and stimulation of peptide YY and pancreatic polypeptide secretion by intraduodenal lipid. Am. J. Physiol. Endocrinol. Metab. 289: E948-E953 [Abstract] [Full Text]
Koegler, F. H., Enriori, P. J., Billes, S. K., Takahashi, D. L., Martin, M. S., Clark, R. L., Evans, A. E., Grove, K. L., Cameron, J. L., Cowley, M. A. (2005). Peptide YY(3-36) Inhibits Morning, but Not Evening, Food Intake and Decreases Body Weight in Rhesus Macaques. Diabetes 54: 3198-3204 [Abstract] [Full Text]
Tighe, S., Dinan, T. (2005). An overview of the central control of weight regulation and the effect of antipsychotic medication. J Psychopharmacol 19: 36-46 [Abstract]
Siahanidou, T., Mandyla, H., Vounatsou, M., Anagnostakis, D., Papassotiriou, I., Chrousos, G. P. (2005). Circulating Peptide YY Concentrations Are Higher in Preterm than Full-Term Infants and Correlate Negatively with Body Weight and Positively with Serum Ghrelin Concentrations. Clin. Chem. 51: 2131-2137 [Abstract] [Full Text]
Stanley, S., Wynne, K., McGowan, B., Bloom, S. (2005). Hormonal Regulation of Food Intake. Physiol. Rev. 85: 1131-1158 [Abstract] [Full Text]
Oesch, S., Degen, L., Beglinger, C. (2005). Effect of a protein preload on food intake and satiety feelings in response to duodenal fat perfusions in healthy male subjects. Am. J. Physiol. Regul. Integr. Comp. Physiol. 289: R1042-R1047 [Abstract] [Full Text]
Daousi, C., MacFarlane, I. A., English, P. J., Wilding, J. P. H., Patterson, M., Dovey, T. M., Halford, J. C. G., Ghatei, M. A., Pinkney, J. H. (2005). Is There a Role for Ghrelin and Peptide-YY in the Pathogenesis of Obesity in Adults with Acquired Structural Hypothalamic Damage?. J. Clin. Endocrinol. Metab. 90: 5025-5030 [Abstract] [Full Text]
Talsania, T., Anini, Y., Siu, S., Drucker, D. J., Brubaker, P. L. (2005). Peripheral Exendin-4 and Peptide YY3-36 Synergistically Reduce Food Intake through Different Mechanisms in Mice. Endocrinology 146: 3748-3756 [Abstract] [Full Text]
Wynne, K., Park, A. J., Small, C. J., Patterson, M., Ellis, S. M., Murphy, K. G., Wren, A. M., Frost, G. S., Meeran, K., Ghatei, M. A., Bloom, S. R. (2005). Subcutaneous Oxyntomodulin Reduces Body Weight in Overweight and Obese Subjects: A Double-Blind, Randomized, Controlled Trial. Diabetes 54: 2390-2395 [Abstract] [Full Text]
Torekov, S. S., Larsen, L. H., Glumer, C., Borch-Johnsen, K., Jorgensen, T., Holst, J. J., Madsen, O. D., Hansen, T., Pedersen, O. (2005). Evidence of an Association Between the Arg72 Allele of the Peptide YY and Increased Risk of Type 2 Diabetes. Diabetes 54: 2261-2265 [Abstract] [Full Text]
Goldstone, A. P., Patterson, M., Kalingag, N., Ghatei, M. A., Brynes, A. E., Bloom, S. R., Grossman, A. B., Korbonits, M. (2005). Fasting and Postprandial Hyperghrelinemia in Prader-Willi Syndrome Is Partially Explained by Hypoinsulinemia, and Is Not Due to Peptide YY3-36 Deficiency or Seen in Hypothalamic Obesity Due to Craniopharyngioma. J. Clin. Endocrinol. Metab. 90: 2681-2690 [Abstract] [Full Text]
Garcia, J. M., Garcia-Touza, M., Hijazi, R. A., Taffet, G., Epner, D., Mann, D., Smith, R. G., Cunningham, G. R., Marcelli, M. (2005). Active Ghrelin Levels and Active to Total Ghrelin Ratio in Cancer-Induced Cachexia. J. Clin. Endocrinol. Metab. 90: 2920-2926 [Abstract] [Full Text]
Ma, L., Tataranni, P. A., Hanson, R. L., Infante, A. M., Kobes, S., Bogardus, C., Baier, L. J. (2005). Variations in Peptide YY and Y2 Receptor Genes Are Associated With Severe Obesity in Pima Indian Men. Diabetes 54: 1598-1602 [Abstract] [Full Text]
Koda, S., Date, Y., Murakami, N., Shimbara, T., Hanada, T., Toshinai, K., Niijima, A., Furuya, M., Inomata, N., Osuye, K., Nakazato, M. (2005). The Role of the Vagal Nerve in Peripheral PYY3-36-Induced Feeding Reduction in Rats. Endocrinology 146: 2369-2375 [Abstract] [Full Text]

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