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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