Plasma Levels of Neuropeptide Y and Peptide YY in Patients Diagnosed with Anorexia Nervosa and Type 2 Diabetes Morbid Obese Subjects
Endocrinology & Metabolic Syndrome

Endocrinology & Metabolic Syndrome
Open Access

ISSN: 2161-1017

+44 20 3868 9735

Research Article - (2012) Volume 1, Issue 1

Plasma Levels of Neuropeptide Y and Peptide YY in Patients Diagnosed with Anorexia Nervosa and Type 2 Diabetes Morbid Obese Subjects

Maria Chiara Masoni*, Claudio Scarpellini, Elena Matteucci, Ester Morelli and Ottavio Giampietro
Department of Internal Medicine, University of Pisa, Pisa, Italy
*Corresponding Author: Maria Chiara Masoni, Department of Internal Medicine, University of Pisa, Via Roma 67, 56126 Pisa, Italy, Tel: +39-050-993629, Fax: +39- 050-993520 Email:


Anorexia Nervosa (AN) and Obesity are prevalent in modern societies. This study evaluate circulating levels of Neuropeptide Y (NPY) and of Peptide Tyrosine-Tyrosine (PYY) in 60 women: 20 affected by AN (Body Mass Index = BMI 15.74 ± 2.09 kg/m2, age 30.19 ± 10.52 yr), 10 restrictor (BMI 14.89 ± 1.64 kg/m2) and 10 binge-purge subtype (BMI 18.27 ± 0.81 kg/m2); 20 affected by severe Obesity (BMI>40 kg/m2; age 33.56 ± 5.2 yr) with type II diabetes with no therapy, and 20 healthy controls (BMI 22.06 ± 0.93 kg/m2, age 32.44 ± 4.35 yr). NPY is higher in AN than obese and controls (70.17 ± 20.84 vs 25.12 ± 7.26 and 52.20 ± 10.88 pmol/L; p<0.001) and lower in obese than controls (p<0.001). PYY is higher in AN than obese and controls (219.77 ± 83.51 vs 116.42 ± 41.42 and 94.97 ± 12.74 pg/ml; p<0.001), with no differences between obese and controls. In AN, NPY and PYY are quite higher (p=0.059; p=0.06) in restrictor (75.77 ± 20.86 pmol/L; 241.78 ± 84.6 pg/ml) than in binge-purge subtype (53.39 ± 8.72 pmol/L; 153.73 ± 29.45 pg/ml). Increase of NPY despite simultaneous PYY increase in AN might be related to reduced sensitivity to PYY inhibitory effect on NPY production or increased production of NPY from sympathetic peripheral nervous system, a finding evident mainly in restrictor AN. In obese PYY is close to controls suggesting a reduced intestinal production of this peptide because of the stimulus of continuous overfeeding, whereas the reduced NPY production could be explained by increased levels of insulin and leptin. Reduced NPY levels suggest that in these obese the overfeeding is not dependent on increased hungry signal, but on inadequate satiety signal.


Anorexia Nervosa (AN) and obesity are prevalent in modern societies. AN is a multifaceted disease characterized by disorganized feeding behavior, food adversion and strong attention to body shape and weight [1], accompanied by psychiatric symptoms such as depression and/or obsessive-compulsive disorder [2,3]. AN is the most common form of eating disorders in western society having a prevalence of 0.1-1% in general population, 0.3% in women and 0.1% in men. This condition largely affects young adolescent women, with between 15 and 25 years old making up 40% of all cases and the risk of mortality is 5–20% [4-7]. Obesity is a chronic condition characterized by an accumulation of body fat. The prevalence of the disease is progressively increasing in industrialized nations as a consequence of adoption of those life style changes typical of the western culture, especially regarding diet and physical inactivity [1,5].

The food intake is regulated by long- and short-term acting mediators [8-12] and involves complicated associations between neuropeptides and other neurotransmitters in the central nervous system (CNS) [13-17]. In people with eating disorders the disturbances of these neuroendocrine pathways could be responsible of frequent symptoms as refusal to eat, denial of hunger, irritability, feeling of physical efficiency up to excessive exercise [2]. Long-term acting mediators are hormonal signals produced by the pancreas such as Insulin, as well by the adipose tissue like Leptin and Adiponectin, all communicating with the brain about body fat and energy storage. These hormones do participate in the long-term regulation of energy homeostasis and body weight maintenance. Short-term acting mediators are peptides produced by enteroendocrine cells interspersed among the gastrointestinal tract; they act through the bloodstream or the vagus nerve on the CNS. These satiety signals [18,19] are meal-related and are effective in maintaining adequate meal size according to the energy expenditure and long-term maintenance of body weight [20,21]. Peptide Tyrosine-Tyrosine (PYY) is the most important anorexigenic substance [22] belonging to the pancreatic polypeptide family [23-25]. Anorexigenic effect is likely the consequence of PYY binding to the Y2 receptor, resulting in presynaptic inhibition of neuropeptide Y (NPY) neurons in the accurate nucleus (ARC) [25-31]. The hypothalamic ARC seems to play a crucial role in receiving and integrating these signals, it is incompletely isolated from the general circulation by the blood–brain barrier, allowing direct access of circulating factors to ARC neurons [32]. NPY is a 36-aminoacid neurotransmitter also belonging to the pancreatic polypeptide family; it is one of the most important orexigenic agents [33]. Animal experimental evidences suggest that NPY is coreleased with norepinephrine (NE) from sympathetic nerve endings and is involved in noradrenergic neurogenic vascular control of skeletal muscle [34]. However, most of NPY neurons are in the ARC: they are inhibited by insulin and/or leptin [35,36] and by PYY [25,37], while they are stimulated by restriction of food, starvation and ghrelin [38]. NPY interacts with the orexigenic Y1 and Y5 receptors in different brain areas [39].

The food intake disorders could be associated to the variation of some neuroendocrine signals that would then be involved in the etiopathogenesis of AN and morbid obesity.

The aim of this study is to measure circulating levels of NPY, a powerful feeding stimulator, and of PYY, inhibitor of NPY neurons as well an anorexigenic peptide, in AN and morbid obesity to evaluate whether peptide disturbances are cause or consequence of eating disorders.

Materials and Methods


The study group involved forty consecutive women attending to the Diet Health Education Clinic of Internal Medicine Department from May 2010 to May 2011: 20 diagnosed with AN according to the criteria of Manual Statistic Diagnostic IV edition (DSM-IV) and 20 diagnosed with no treated type 2 diabetes morbid obese subjects.

Ten of 20 (50%) AN subjects were restrictors, 10 were binge-purge subtype.

Twenty healthy, normal weight ages matched women recruited from the Department staff were enrolled as control group (table 1).

AN restrictor n=10 AN
binge-purge n=10
Morbid obese n=20 Controls n=20
Age (years) 30.2±10.5 32.4±11.4 23.5±0.6 33.6±5.2 32.4±4.3
Body Weight (kg) 41.6±5.5 39.2±3.1 48.9±4.5 122.8±13.8 66.2±5.8
BMI (kg/m2) *
18.3±0.8 **
NPY (pmol/L) *
75.8±20.9 53.4±8.7 **
PYY (pg/ml) *
241.8±84.6 153.7±29.4 116.4±41.4 95±12.7
BMI: * p<0.001 AN vs morbid obese/controls; ** p<0.001 morbid obese vs controls;
*** p<0.001 restrictor vs binge/purge AN subtypes
NPY: * p<0.001 AN vs morbid obese/controls; ** p<0.001 morbid obese vs controls
PYY: * p<0.001 AN vs morbid obese/controls

Table 1: Study subjects’ characteristics and NPY and PYY plasma concentrations.

All subjects gave informed consent and the ethical committee of the hospital approved the study proposal.

Data collection

Age was defined as age in years at the time of the medical visit. Weight and height were performed in the morning before 8 a.m. after an overnight fast (12 h). The body mass index (BMI) was calculated as body weight/height2 (in kg/m2). The depression and the obsessivecompulsive disorder were employed by Beck Depression Inventory (BDI). Fasting venous blood samples were collected into EDTA (ethylenediaminetetraacetic acid) to 6% (100 μl for 5 ml of blood)- treated tubes and immediately centrifuged at 4°C for 15 min. Plasma was divided into aliquots and stored at -70°C until assay.

Laboratory analysis

NPY in plasma samples was assayed by a competitive radioimmunoassay (RIA) (Euro-Diagnostic Sweden) using an antiserum raised against synthetic NPY conjugated to bovine thyreoglobulin. NPY in standards and samples competes with 125I-labelled NPY in binding to the antibodies. 125I–NPY binds in a reverse proportion to the concentration of NPY in standards and samples. Antibody-bound 125I–NPY is separated from the unbound fraction by using a double antibody coupled to solid phase. The radioactivity of the antibodybound 125I–NPY is measured. The antiserum used in this method crossreacts less than 2.0% with human PYY. The intra- and inter-assay variability for plasma NPY was 5.0% and 8.4%, respectively, and the lower limit of sensitivity was 3 pmol/l.

Plasma PYY concentrations were measured using a human PYY (3-36) RIA (DRG Germany), with 100% cross-reactivity with the two biologically active forms of PYY (1-36 human PYY and 3-36 human PYY) and no cross-reactivity with NPY, pancreatic polypeptide, insulin, glucagon, amylin amide, or substance P. Intra and inter-assay coefficient of variation of the assay were 5.6% and 6.7% respectively, and the lower limit of detection was 2.8 pg/ml.

Statistical analysis

All data were expressed as mean ± standard deviation of the mean. Results were analyzed by a commercial software package (NCSS) using unpaired t test for single comparisons (all data were normally distributed). Correlations were sought by linear regression analysis. Statistical significance was defined as P < 0.05.


By BDI, eleven of twenty (55%) AN presented mild depression, nine patient (45%) had obsessive-compulsive disorder. Morbid obese patients had no depressive symptomatology.

BMI was significantly lower (p<0.001) in AN patients than in no-treated type 2 diabetes morbid obese subjects and normal weight healthy subjects.

BMI of restrictor was significantly lower (p < 0.001) than bingepurge (14.89 ± 1.64 vs 18.27 ± 0.81 kg/m2) subtype.

Higher NPY level was observed in AN than type 2 diabetes morbid obese and normal weight subjects (70.2 ± 20.8 vs 25.1 ± 7.3 and 52.2 ± 10.9 pmol/L, respectively; p<0.001) and lower in type 2 diabetes morbid obese and normal weight subjects (25.1 ± 7.3 vs 52.2 ± 10.9 pmol/L; p<0.001).

Higher PYY was also shown in AN than morbid obese and normal weight (219.8 ± 83.5 vs 116.4 ± 41.4 and 95 ± 12.7 pg/ml, respectively; p<0.001), while in type 2 morbid obese and normal weight was similar.

We observed tendency to higher NPY and PYY levels in restrictor than binge-purge AN subtype (75.8 ± 20.9 pmol/L vs 53.4 ± 8.7 pmol/L and 241.8 ± 84.6 pg/ml vs 153.7 ± 29.4 pg/ml, respectively) (table 1).

There was an inverse correlation between BMI of patients and the NPY (r= -0.75; p <0.001) as well PYY (r= -0.40; p<0.001) concentrations (Figures 1 and 2). Direct correlation exists between NPY and PYY plasma levels (r= 0.3, p<0.05) (Figure 3).


Figure 1: Correlation between BMI and NPY in all subjects.


Figure 2: Correlation between BMI and PYY in all subjects.


Figure 3: Correlation between NPY and PYY in all subjects.


Studies on the role of the chemical mediators and their mechanisms in the regulation of food intake have been ongoing for several years but results are still conflicting [38,40,41].

In the present paper, we found in anorectic’s women concomitant increase of both NPY and PYY concentrations. This unexpected result might be related to reduced sensitivity of Y2 receptors to PYY inhibitory effect on NPY production, or to increased production of NPY from sympathetic peripheral nervous system, a finding frequently reported mainly in restrictor AN.

In anorectic patients NPY, although elevated, could not carry on its orexigenic activity, as if a reduced responsivity of Y1 and Y5 receptors could be operative with a mechanism similar to the insulin resistance in DMT2 and obesity [42]. Alternatively NPY, although operative, could not succeed to stimulate eating because other signals interfere. At this regard, we did find that serotonin in AN is higher than in type 2 diabetes morbid obese patients and normal weight healthy subjects (unpublished data).

In binge-purges NPY was found lower than in restrictors. Since the food intake reduction in binge-purges alternates with binging [2-4,43], NPY production is irregular, thus the resistance of Y1-Y5 receptors unlikely may develop. Moreover, in binge-purges serotonin (unpublished data) is lower than in restrictors, this allowing rise of food intake.

These results, together considered, address the hypothesis that despite in AN there is an hyper-production both of NPY and PYY [44,45], neither seems working properly, because of the receptors desensitization. Since NPY and PYY bind to the receptors of the same family [25,39], they could be inactivated by the same pathways.

Finally, we did not find any correlations between mental symptoms and hormone concentrations in anorectic patients.

In morbid obese subjects, PYY is close to controls suggesting a reduced intestinal production because of continuous overfeeding, whereas the reduced NPY production could be explained by increased levels of insulin and leptin. Reduced PYY and NPY levels indicate that in these patients the overfeeding is not dependent on increased hungry signal, but on inadequate satiety signal. The PYY deficiency may contribute to the pathogenesis of obesity [46]. As a support, PYY administration leads to a decrease in food intake in rodent models [47] as well as in obese adults [48].

As suggested [45], changes in chemical mediator’s activity, some of them still unknown, lead to food intake disorders which trigger a vicious circle; moreover the simultaneous hyper-production of orexigenic and anorexigenic signals sends confusing messages to hypotalamic areas [45].

Further, BMI is closely correlated with PYY concentrations, as well NPY, indicating a continuum between nutritional status and neuropeptides behavior.

In conclusion, for the first time this study shows significant differences between restrictor and binge-purge AN subtype as for as the evaluated parameters are concerned. The better nutritional status should positively influence the plasma levels of chemical mediators.


We thank Stefania Favilla, Claudia D’Alessandro, Annamaria Martinelli, Claudia Mammoli for their technical assistance. We are deeply indebted to Daniela Testa, Sandra Rinaldi, Maria Graziella Cesari, Alba Di Giusto, Barbara Simoni for their kindly participation to the study.


  1. Schweiger U, Fichter M (1997) Eating disorders: clinical presentation, classification and etiologic models. In: D.C. Jimerson and W.H. Kaye, Editors, Balliere's clinical psychiatry, Balliere's Tindall 199-216.
  2. Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) (1994) 4th ed. Washington DC: American Psychiatric Association .
  3. Stoving RK, Hangaard J, Hansen-Nord M, Hagen C (1999) A review of endocrine changes in anorexia nervosa. J Psychiatric Research 33: 139-152
  4. Nielsen S, Moller-Madsen S, Isager T, Jorgensen J, Pagsberg K, et al. (1998) Standardized mortality in eating disorders-a quantitative summary of previously published and new evidence. J Psychosom Res 44: 413-434.
  5. Herzog DB, Greenwood DN, Dorer DJ, Flores AT, Ekeblad ER, et al. (2000) Mortality in eating disorders: a descriptive study. Int J Eat Disord 28: 20-26.
  6. Kendler KS, MacLean C, Neale M, Kessler R, Heath A, et al. (1991) The genetic epidemiology of bulimia nervosa. Am J Psychiatry 148: 1627-1637.
  7. Smith GP (2005) Controls of food intake. In: Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ (Eds), Modern Nutrition in health and disease. (10th ed) Lippincott Williams e Wilkins 707-719.
  8. Asakawa A, Inui A, Goto K, Yuzuriha H, Takimoto Y et al. (2002) Effects of agouti-related protein, orexin and melanin-concentrating hormone on oxygen consumption in mice. Int J Mol Med 10: 523-525.
  9. Badman MK, Flier JS (2005) The gut and the energy balance: visceral allies in the obesity wars. Science, 307: 1909-1914.
  10. Costentin J (2004) Physiological and neurobiological elements of food intake. Ann Pharm Fr 62: 92-102.
  11. Seeley RJ, Woods SC (2003) Monitoring of stored and available fuel by the CNS: implications for obesity. Nat Rev Neurosci 4: 901-909.
  12. Woods SC (2004) Gastrointestinal satiety signals I. An overview of gastrointestinal signals that influence food intake. Am J Physiol 286: G7-G13
  13. Chaudhri OB, Field BCT, Bloom SR (2006) From Gut to Mind-Hormonal Satiety Signals and Anorexia Nervosa. J Clin Endocrinol Metab 91: 797-798.
  14. Smith GP (2000) The controls of eating: a shift from nutritional homeostasis to behavioral neuroscience. Nutrition 16: 814-820.
  15. Konturek SJ, Konturek JW, Pawlik T, Brzozowski T (2004) Brain-gut axis and its role in the control of food intake. J Physiol Pharmacol 55: 137-54
  16. Schwartz GJ (2006) Integrative capacity of the caudal brainstem in the control of food intake. Philos Trans R Soc Lond B Biol Sci 361: 1275-1280.
  17. King PJ (2005) The hypothalamus and obesity. Curr Drug Targets 6: 225-240.
  18. Strubbe JH, van Dijk G (2002) The temporal organization of ingestive behaviour and its interaction with regulation of energy balance. Neurosci Biobehav Rev 26: 485-498.
  19. Strader AD, Woods SC (2005) Gastrointestinal hormones and food intake. Gastroenterology 128: 175-191
  20. Ramos EJ, Meguid MM, Campos AC, Coelho JC (2005) Neuropeptide Y, alpha-melanocyte-stimulating hormone, and monoamines in food intake regulation. Nutr 21: 269-79.
  21. Gerstein DE, Woodward-Lopez G, Evans AE, Kelsey K, Drewnowski A (2004) Clarifying concepts about macronutrients'effects on satiation and satiety. J Am Diet Ass 104: 1151-1153.
  22. Morley JE, Levine AS, Grace M, Kneip J (1985) Peptide YY (PYY), A potent orexigenic agent. Brain Res 200-203.
  23. Tatemoto K, Mutt V (1980) Isolation of two novel candidate hormones using a chemical method for finding naturally occurring polypeptides. Nature 285: 417-418.
  24. Hanusch-Enserer U, Roden M (2005) News in gut-brain communication: a role of peptide YY (PYY) in human obesity and following bariatric surgery? Eur J Clin Invest 35: 425-430.
  25. le Roux CW, Bloom SR (2005) Peptide YY, appetite and food intake. Proc Nutr Soc 64: 213-216.
  26. Lin HC, Chey WY (2003) Cholecystokinin and peptide YY are released by fat in either proximal or distal small intestine in dogs. Regul Pept 114: 131-135.
  27. Cox HM (2007) Peptide YY: A neuroendocrine neighbor of note. Peptides 28: 345-351.
  28. McGowan BMC, Bloom SR (2004) Peptide YY and appetite control. Curr Opin Pharmacol 4: 583-588.
  29. Sloth B, Holst JJ, Flint A, Gregersen NT, Astrup A (2007) Effects of PYY1-36 and PYY3-36 on appetite, energy intake, energy expenditure, glucose and fat metabolism in obese and lean subjects. Am J Physiol Endocrinol Metab 292: E1062-E1068.
  30. Nakahara T, Kojima S, Tanaka M, Yasuhara D, Harada T, et al. (2006) Incomplete restoration of the secretion of ghrelin and PYY compared to insulin after food ingestion following weight gain in anorexia nervosa. J Psychires 41: 814-820.
  31. Broberger C, Landry M, Wong H, Walsh JN, Hokfelt T (1997) Subtypes Y1 and Y2 of the neuropeptide Y receptor are respectively expressed in pro-opiomelanocortin- and neuropeptide-Y-containing neurons of the rat hypothalamic arcuate nucleus. Neuroendocrinology 66: 393-408.
  32. Williams G, Bing C, Cai XJ, Harrold JA, King PJ, et al. (2001) The hypothalamus and the control of energy homeostasis: different circuits, different purposes. Physiol Behav 74: 683-691.
  33. Gareth W, Xue JC, Joanne CE, Joanne AH (2004) Anabolic neuropeptides. Physiol Behav 81: 211-222.
  34. Misra M, Miller KK, Tsai P, Gallagher K, Lin A, et al. (2006) Elevated Peptide YY Levels in Adolescent Girls with Anorexia Nervosa. J Clin Endocrinol Metab 91: 1027-1033.
  35. Kahan T, Taddei S, Pedrinelli R, Hjemdahl P, Salvetti A (1992) Noradrenergic sympathetic vascular control of the human forearm in hypertension: possible involvement of neuropeptide Y. J Cardivasc Pharmacol 19: 587-592.
  36. Wang J, Leibowitz KL (1997) Central insulin inhibits galanin and neuropeptide Y gene expression and peptide release in intact rats. Brain Res 777: 231-236.
  37. Schwartz MW, Figlewicz DP, Baskin DG, Woods SC, Porte DJ (1992) Insulin in the brain: a hormonal regulator of energy balance. Endocr Rev 13: 387-414.
  38. Le Roux C, Bloom S (2005) Peptide YY, appetite and food intake. Proc Nutr Soc 64:213-216.
  39. Stock S, Leichner P, Wong ACK, Ghatei MA, Kieffer TJ, et al. (2005) Ghrelin, Peptide YY, Glucose-Dependent Insulinotropic Polypeptide, and Hunger Responses to a Mixed Meal in Anorexic, Obese, and Control Female Adolescents. J C Endocrinol Metab 90: 2161-2168.
  40. Feletou M, Levens NR (2005) Neuropeptide Y2 receptors as drug targets for the central regulation of body weight. Curr Opin Investig Drugs 6: 1002-1011.
  41. Kojima S, Nakahara T, Nagai N, Muranaga T, Tanaka M, et al. (2005) Altered ghrelin and peptide YY responses to meals in bulimia nervosa. Clin Endocrinol 62: 74-78.
  42. Fisher M, Golden NH, Katzman DK, Kreipe RE, Rees J, et al. (1995) Eating disorders in adolescents: a background paper. J Adolesc Health 16: 420-437.
  43. Flier JS (2004) Obesity wars molecular progress confronts an expanding epidemic. Cell 116: 337-350.
  44. Kaye WH, Frank GK, Boiler UF, Henry SE, Meltzer CC, et al. (2005) Serotonin alterations in anorexia and bulimia nervosa: New insights from imaging studies. Physiol Behav 85: 73-81.
  45. Kaye WH, Barbarich NC, Putnam K, Gendall KA, Fernstrom J, et al. (2003) Anxiolytic effects of acute Tryptophan depletion in anorexia nervosa. Int J Eat Disord 33: 257-267.
  46. Palasz A (2004) Functional disturbances of the Hypothalamus in patients with anorexia nervosa. Psychiatr Pol 38: 1001-1009.
  47. Batterham R, Cohen M, Ellis S, Le Roux C, Withers D, et al. (2003) Inhibition of food intake in obese subjects by peptide YY3-36. N Engl J Med 349: 941-948.
  48. Challis B, Pinnock S, Coll A, Carter R, Dickson S, et al. (2003) Acute effects of PYY3-36 on food intake and hypothalamic neuropeptide expression in the mouse. Biochem Biophys Res Commun 311: 915-919.
  49. Riediger T, Bothe C, Becskei C, Lutz T (2004) Peptide YY directly inhibits ghrelin-activated neurons of the arcuate nucleus and reverses fasting-induced c-Fos expression. Neuroendocrinology 9: 317-326
Citation: Masoni MC, Scarpellini C, Matteucci E, Morelli E, Giampietro O (2012) Plasma Levels of Neuropeptide Y and Peptide YY in Patients Diagnosed with Anorexia Nervosa and Type 2 Diabetes Morbid Obese Subjects. Endocrinol Metabol Syndrome 1:104.

Copyright: © 2012 Masoni MC, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.