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Title: Appetite Modulating Peptide Inhibits Food Intake in Obese and Lean Individuals

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N Eng J Med 2003;349:941-948.
09/05/2003 04:14:00 PM
By Joene Hendry

Both appetite and food intake were inhibited following the infusion of peptide YY[_3-36 (PYY) in obese and lean individuals. PYY modulates appetite circuits in the hypothalamus and, similar to leptin, reduces food intake. While obese patients show a marked resistance to the action of leptin, they do not show a similar resistance to PYY. "These findings suggest that PYY may be a useful treatment for obesity," writes Rachel L. Batterham, MB, BS, and colleagues from the Imperial College Faculty of Medicine at Hammersmith Campus, London, United Kingdom. The investigators compared the effects of PYY infusion on appetite, food intake, and plasma levels of PYY in 12 obese (mean body mass index 33.0) and 12 lean (mean body mass index 20.5) individuals in a double-blind crossover study. The groups consisted of equal numbers of non-smoking men and women with stable body weight for at least 3 months. The subjects took no medications except oral contraceptives, had no current medical or psychiatric illness, and were mean age of 29 and 27.3 years in the obese and lean groups, respectively. Participants underwent a 90-minute infusion of PYY (2 nmol per square meter of body-surface area) or saline following a standardized 48-hour food intake and a 12-hour fast. Two hours after infusion the participants ate until satisfied from an identical buffet lunch. The investigators collected blood samples every 30 minutes throughout the study. Compared with after saline infusion, the obese group showed a 29.9% reduction in caloric intake after PYY infusion. Similarly, caloric intake was reduced by 31.1% after PYY when compared with saline infusion among the lean group. Food diaries from the 12-hour post-infusion periods show that the obese group consumed 26.3% fewer calories after PYY infusion compared with saline infusion. The lean group consumed 33.7% fewer calories after PYY infusion compared with saline infusion. The overall 24-hour calorie intake was reduced by 16.5% in the obese group and 23.5% in the lean group following PYY infusion compared with saline infusion. The participants reported no effect on food palatability and no other side effects from PYY infusion. "We found that fasting PYY levels were lower in the obese group than in the lean group and that there was a negative correlation between fasting PYY levels and body-mass index," the authors write. They also found that postprandial PYY release was lower in obese than in lean subjects, even though the obese subjects consumed more calories at the buffet lunch. The investigators conclude, "these findings are consistent with the hypothesis that a deficiency in circulating PYY may be involved in the pathogenesis of obesity."

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