The gut hormone fragment peptide YY _3-36 (PYY) is known to reduce appetite and food intake when given to subjects of normal weight as well as to rodents. The authors investigated whether obese subjects were also sensitive to the anorectic effects of PYY. They compared the effects of this peptide by infusing it into 12 obese and 12 lean subjects in a double-blind, placebo-control, crossover study, and measured the effects on appetite, food intake as well as plasma levels of PYY, ghrelin, leptin and insulin. Caloric intake during a buffet lunch two hours after the infusion of PYY was significantly decreased by 30% in the obese and by 31% in the lean subjects. PYY infusion also caused a significant decrease in the cumulative 24-hour calorie intake in both obese and lean subjects. The average decrease in the food ingestion was about one-third of the calories, as compared to the amount consumed the day prior to the infusion. However, food intake from 0-12 hours following PYY administration was more markedly reduced than that ingested from 12-24 hours after the infusion. The administration of PYY also reduced plasma levels of the appetite stimulatory hormone, ghrelin. Endogenous fasting and postprandial levels of PYY were significantly lower in obese subjects as compared to the non-obese group. Furthermore, the fasting PYY levels correlated negatively with BMI. The authors concluded that obese subjects were not resistant to the anorectic effects of PYY and suggested that a deficiency of PYY may contribute to the pathogenesis of obesity in humans.

Batterham RL, et al. Inhibition of food intake in obese subjects by peptide YY _3-36. N Engl J Med 2003;349:941-948.

Editor's Comment: PYY is secreted postprandially, in proportion to the calories ingested, by endocrine L cells lining the distal small bowel and colon. PYY leads to a decrease food intake by inhibiting gut motility and increasing satiety. In this study, PYY infusion reduced hunger in both the obese and the lean individuals. These effects were directly related to the action of PYY, as there were no effects on the palatability of meals, feelings of well being, or the presence of nausea. This peptide is one of the many signals that have been recently identified providing short-term information to the hindbrain and hypothalamus regarding hunger and satiety. Other gut hormones, such as cholecystokinin and ghrelin, also play a role in communicating with the hypothalamus and brain stem to stimulate or reduce the appetite. In this issue of GGH there is a review of ghrelin , the hunger hormone, acting on growth hormone secretagogue receptors and its pathophysiologic role in obesity related diseases.1 However, the regulatory controls of food intake are more complex and involve other endocrine functions of adipose tissue, principally leptin, and appetite controlling genes as previously reviewed .2 However, PYY signal in satiety appears to play a role in obesity in humans and could be thought of as a therapeutic agent; a hope that was not shared by leptin, as in obesity there is marked resistance to the actions of this hormone. A graphic depicting the complex interactions among hormonal and neural pathways that regulate food intake and body fat mass3 is shown below (Figure).

Fima Lifshitz , MD

References - (linked to )

1. Casanueva FF, Dieguez C. GGH 2004;20:1-8.
2. Diamond F. GGH 2002; 18:17 -22.
3. Korner J, Liebel R. N Eng J Med 2003;1349:926-928.