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Effect of Human Body Weight Changes on Circulating Levels of Peptide YY and Peptide YY_3–36

Departments of Psychiatry and Medicine (P.T.P., J.K., T.R.C., T.V., D.A.D., T.K., S.C.B., M.H.T.), Obesity Research Center, University of Cincinnati–Genome Research Institute, Cincinnati, Ohio 45237; Department of Physiology (J.K.), Monash University, Melbourne 3800, Australia; Center for Psychosomatic Medicine (U.C.), D-83209 Prien, Germany; German Institute of Human Nutrition (H.J.R., M.M., A.F.H.P., C.K., M.O.W., J.S.), 10551 Nuthetal, Germany; Department of Preventive Medicine (C.K.), University of Southern California, Los Angeles, California 90089; and Department of Gastroenterology (B.O.), University Hospital, D-81377 Munich, Germany

Address all correspondence and requests for reprints to: Matthias H. Tschöp, M.D., Associate Professor, Departments of Psychiatry and Medicine, University of Cincinnati, Office E-217, Genome Research Institute, 2170 East Galbraith Road, Cincinnati, Ohio 45237. E-mail: tschoemh{at}ucmail.uc.edu.

Background: Recent findings suggest that low plasma peptide YY (PYY) levels may contribute to diet-induced human obesity and justify PYY replacement therapy. Although the pharmacological value of PYY is controversial, further study of the secretion of the precursor PYY_1–36 and the pharmacologically active PYY_3–36 is indicated to determine the potential role in energy balance regulation.

Aim: Our objective was to determine the effects of acute and chronic changes in human body weight on circulating levels of the putative satiety hormone peptide YY.

Design: Total plasma PYY levels (PYY_1–36 + PYY_3–36) were measured in 66 lean, 18 anorectic, 63 obese, and 16 morbidly obese humans. In addition, total PYY was measured in 17 of the obese patients after weight loss and in the 18 anorectic patients after weight gain. Fasting PYY_3–36 levels were measured in 17 lean and 15 obese individuals.

Results: Fasting total plasma PYY levels were highest in patients with anorexia nervosa (80.9 ± 12.9 pg/ml, P < 0.05) compared with lean (52.4 ± 4.6 pg/ml), obese (43.9 ± 3.8 pg/ml), or morbidly obese (45.6 ± 11.2 pg/ml) subjects. In obese patients, weight loss of 5.4% was associated with a 30% decrease in fasting total PYY plasma levels. In anorectic patients, weight gain had no effect on fasting PYY. PYY_3–36 levels did not differ between lean (96.2 ± 8.6 pg/ml) and obese (91.5 ± 6.9 pg/ml) subjects.

Conclusion: Our findings do not support a role for abnormal circulating PYY in human obesity. We conclude that circulating PYY levels in humans are significantly elevated in anorexia nervosa and, given the controversially discussed anorectic effect of PYY, could theoretically contribute to that syndrome.

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