We found that obese subjects were not resistant to the anorectic effects of PYY. Endogenous PYY levels were low in the obese subjects, suggesting that PYY deficiency may contribute to the pathogenesis of obesity.

Objective To compare changes over time in waist circumference (a measure of central fatness) and body mass index (a measure of overall obesity) in British youth. Design Representative cross sectional surveys in 1977, 1987, and 1997. Setting Great Britain. Participants Young people aged 11-16 years surveyed in 1977 (boys) and 1987 (girls) for the British Standards Institute (n=3784) and in 1997 (both sexes) for the national diet and nutrition survey (n=776). Main outcome measures Waist circumference, expressed as a standard deviation score using the first survey as reference, and body mass index (weight(kg)/height(m)2 ), expressed as a standard deviation score against the British 1990 revised reference. Overweight and obesity were defined as the measurement exceeding the 91st and 98th centile, respectively. Results Waist circumference increased sharply over the period between surveys (mean increases for boys and girls, 6.9 and 6.2 cm, or 0.84 and 1.02 SD score units, P < 0.0001). In centile terms, waist circumference increased more in girls than in boys. Increases in body mass index were smaller and similar by sex (means 1.5 and 1.6, or 0.47 and 0.53 SD score units, P < 0.0001). Waist circumference in 1997 exceeded the 91st centile in 28% (n=110) of boys and 38% (n=147) of girls (against 9% for both sexes in 1977-87, P < 0.0001), whereas 14% (n=54) and 17% (n=68), respectively, exceeded the 98th centile (3% in 1977-87, P < 0.0001). The corresponding rates for body mass index in 1997 were 21% (n=80) of boys and 17% (n=67) of girls exceeding the 91st centile (8% and 6% in 1977-87) and 10% (n=39) and 8% (n=32) exceeding the 98th centile (3% and 2% in 1977-87). Conclusions Trends in waist circumference during the past 10-20 years have greatly exceeded those in body mass index, particularly in girls, showing that body mass index is a poor proxy for central fatness. Body mass index has therefore systematically underestimated the prevalence of obesity in young people.

Pancreatic polypeptide (PP) is a gut hormone released from the pancreas in response to ingestion of food. Plasma PP has been shown to be reduced in conditions associated with increased food intake and elevated in anorexia nervosa. In addition peripheral administration of PP has been shown to decrease food intake in rodents. These findings suggest that PP may act as a circulating factor that regulates food intake. Therefore we investigated the effect of intravenous infusion of PP (10 pmol/kg/min) on appetite and food intake in a randomised double-blind placebo-controlled crossover study in ten healthy volunteers. Infusion of PP reduced appetite and decreased the energy intake at a buffet lunch two hours post-infusion by 21.8 +/- 5.7% (P < 0.01). More importantly the inhibition of food intake was sustained, such that energy intake, as assessed by food diaries, was significantly reduced both the evening of the study and the following morning. Overall PP infusion reduced cumulative 24-hour energy intake by 25.3 +/- 5.8%. In conclusion our data demonstrates that PP causes a sustained decrease in both appetite and food intake.

Oxyntomodulin (OXM) is released from the gut postprandially, in proportion to energy intake, and circulating levels of OXM are elevated in several conditions associated with anorexia. Central injection of OXM reduces food intake and weight gain in rodents, suggesting that OXM signals food ingestion to hypothalamic appetite-regulating circuits. We investigated the effect of iv OXM (3.0 pmol/kg.min) on appetite and food intake in 13 healthy subjects (body mass index, 22.5 +/- 0.9 kg/m(2)) in a randomized, double-blind, placebo-controlled, cross-over study. Infusion of OXM significantly reduced ad libitum energy intake at a buffet meal (mean decrease, 19.3 +/- 5.6%; P < 0.01) and caused a significant reduction in scores for hunger. In addition, cumulative 12-h energy intake was significantly reduced by infusion of OXM (mean decrease, 11.3 +/- 6.2%; P < 0.05). OXM did not cause nausea or affect food palatability. Preprandial levels of the appetite-stimulatory hormone, ghrelin, were significantly suppressed by OXM (mean reduction, 44 +/- 10% of postprandial decrease; P < 0.0001). Elevated levels of endogenous OXM associated with disorders of the gastrointestinal tract may contribute to anorexia.