Endocrine Abstracts (2004) 7 P42

PYY deficiency may reinforce obesity

CW Le Roux1, SJB Aylwin2, RL Batterham1, CM Borg3, K Wynne1, C Hunt1, F Coyle1, MA Ghatei1, A Patel3 & SR Bloom1

1Department of Metabolic Medicine, Hammersmith Hospital, Imperial College London, UK; 2Department of Endocrinology, King's College Hospital, London, UK; 3Department of Surgery, King's College Hospital, London, UK.

Background: The gut hormone PYY3-36 (PYY) is released into the circulation after eating and physiologically inhibits food intake. Obese and lean subjects are equally sensitive to this effect, however fasting levels of PYY are reduced in obese subjects.

Methods: We investigated the postprandial PYY response and satiety response using a visual analogue scale (VAS) to 6 test meals of increasing calorie content in 20 lean and 20 obese subjects. We also infused 12 volunteers with multiple doses of PYY to test the effect on satiety. Finally we compared the PYY response in 12 patients who had gastric bypass or gastric banding surgery.

Results: Both lean and obese subjects had a rise in PYY response to increasing calories. Obese subjects however, had inappropriately low levels of satiety and an attenuated PYY response at each calorie level. Thus a doubling in the meal calorie content was required to achieve equivalent PYY levels to those observed in lean subjects. Infusions of increasing doses of PYY produced a graded inhibition of appetite and food intake. Subjects treated surgically by gastric bypass had a significant reduction in appetite and an early and increased PYY response at 60 min following a test meal compared to lean and obese controls and patients following gastric banding surgery.

Conclusion: Obese individuals thus have a functional PYY deficiency and reduced satiety. The multiple infusion study suggested that the lower post-prandial PYY levels in obesity might result in an increase in food intake of approximately 10%. Patients post gastric bypass surgery have an exaggerated PYY response which may relate to their reduced appetite and dramatic weight loss.

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