Effect of human body weight changes on circulating levels of peptide YY and peptide YY3-36.

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.

[1]  K. Wynne,et al.  Attenuated peptide YY release in obese subjects is associated with reduced satiety. , 2006, Endocrinology.

[2]  F. Casanueva,et al.  Regulation of peptide YY levels by age, hormonal, and nutritional status. , 2004, Obesity research.

[3]  D. Allison,et al.  PYY3‐36 as an anti‐obesity drug target , 2005, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[4]  S. Bloom,et al.  Ghrelin, peptide YY, glucose-dependent insulinotropic polypeptide, and hunger responses to a mixed meal in anorexic, obese, and control female adolescents. , 2005, The Journal of clinical endocrinology and metabolism.

[5]  M. Maffei,et al.  Positional cloning of the mouse obese gene and its human homologue , 1994, Nature.

[6]  M. Maffei,et al.  Positional cloning of the mouse obese gene and its human homologue , 1995, Nature.

[7]  J M Polak,et al.  Human distribution and release of a putative new gut hormone, peptide YY. , 1985, Gastroenterology.

[8]  J. Shively,et al.  Characterization of two forms of peptide YY, PYY(1–36) and PYY(3–36), in the rabbit , 1994, Peptides.

[9]  A. Klibanski,et al.  Elevated peptide YY levels in adolescent girls with anorexia nervosa. , 2006, The Journal of clinical endocrinology and metabolism.

[10]  A. Leiter,et al.  Peptide YY. Structure of the precursor and expression in exocrine pancreas. , 1987, The Journal of biological chemistry.

[11]  D. Allison,et al.  Physiology: Does gut hormone PYY3–36 decrease food intake in rodents? , 2004, Nature.

[12]  T. Adrian,et al.  Effect of peptide YY on gastric, pancreatic, and biliary function in humans. , 1985, Gastroenterology.

[13]  S. Ashley,et al.  Peptide YY is a physiological regulator of water and electrolyte absorption in the canine small bowel in vivo. , 1993, Gastroenterology.

[14]  M. Tschöp,et al.  Ghrelin induces adiposity in rodents , 2000, Nature.

[15]  C. Beglinger,et al.  Two molecular forms of Peptide YY (PYY) are abundant in human blood: characterization of a radioimmunoassay recognizing PYY 1–36 and PYY 3–36 , 1994, Regulatory Peptides.

[16]  C. H. Chen,et al.  Central inhibitory action of peptide YY on gastric motility in rats. , 1995, The American journal of physiology.

[17]  T. Pedrazzini,et al.  Chronic administration of neuropeptide Y into the lateral ventricle of C57BL/6J male mice produces an obesity syndrome including hyperphagia, hyperleptinemia, insulin resistance, and hypogonadism , 2001, Molecular and Cellular Endocrinology.

[18]  M. Pelleymounter,et al.  Effects of the obese gene product on body weight regulation in ob/ob mice. , 1995, Science.

[19]  J. Rehfeld,et al.  Influence of meal composition on postprandial peripheral plasma concentrations of vasoactive peptides in man. , 1996, Scandinavian journal of clinical and laboratory investigation.

[20]  R. Liddle,et al.  Inhibitory regulation of rat exocrine pancreas by peptide YY and pancreatic polypeptide. , 1989, The American journal of physiology.

[21]  Mohammad A Ghatei,et al.  Inhibition of food intake in obese subjects by peptide YY3-36. , 2003, The New England journal of medicine.

[22]  R. Considine,et al.  Serum immunoreactive-leptin concentrations in normal-weight and obese humans. , 1996, The New England journal of medicine.

[23]  T. Adrian,et al.  Proliferative effects of 'fibre' on the intestinal epithelium: relationship to gastrin, enteroglucagon and PYY. , 1987, Gut.

[24]  T. Hökfelt,et al.  Peptide YY (PYY)-immunoreactive neurons in the lower brain stem and spinal cord of rat. , 1985, Acta physiologica Scandinavica.

[25]  D. Keire,et al.  Structure and receptor binding of PYY analogs , 2002, Peptides.

[26]  M. Nakazato,et al.  Ghrelin is a growth-hormone-releasing acylated peptide from stomach , 1999, Nature.

[27]  M. Bessler,et al.  Effects of Roux-en-Y gastric bypass surgery on fasting and postprandial concentrations of plasma ghrelin, peptide YY, and insulin. , 2005, The Journal of clinical endocrinology and metabolism.

[28]  Claude Bouchard,et al.  Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults. , 1998, WMJ : official publication of the State Medical Society of Wisconsin.

[29]  Rachel L. Batterham,et al.  Gut hormone PYY3-36 physiologically inhibits food intake , 2002, Nature.

[30]  J. Chan,et al.  Peptide YY levels are decreased by fasting and elevated following caloric intake but are not regulated by leptin , 2005, Diabetologia.

[31]  T. Adrian,et al.  Meal‐induced secretion of gastrointestinal regulatory peptides is not affected by sleep , 1997, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[32]  R. Batterham,et al.  The Gut Hormone Peptide YY Regulates Appetite , 2003, Annals of the New York Academy of Sciences.

[33]  T. Adrian,et al.  Effects of an elemental diet, inert bulk and different types of dietary fibre on the response of the intestinal epithelium to refeeding in the rat and relationship to plasma gastrin, enteroglucagon, and PYY concentrations. , 1987, Gut.

[34]  A. Patriti,et al.  Gut hormone profiles following bariatric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters. , 2007, Annals of surgery.

[35]  M. Nakazato,et al.  Altered ghrelin and peptide YY responses to meals in bulimia nervosa , 2005, Clinical endocrinology.

[36]  H. Jang,et al.  Peptide YY is secreted after oral glucose administration in a gender-specific manner. , 2005, The Journal of clinical endocrinology and metabolism.