Login to MyKarger

New to MyKarger? Click here to sign up.

Login with Facebook

Forgot your password?

Authors, Editors, Reviewers

For Manuscript Submission, Check or Review Login please go to Submission Websites List.

Submission Websites List

Institutional Login
(Shibboleth or Open Athens)

For the academic login, please select your country in the dropdown list. You will be redirected to verify your credentials.

Clinical Study

Editor's Choice - Free Access

The Role of Ghrelin, Neuropeptide Y and Leptin Peptides in Weight Gain after Deep Brain Stimulation for Parkinson’s Disease

Markaki E.a · Ellul J.b · Kefalopoulou Z.a · Trachani E.b · Theodoropoulou A.c · Kyriazopoulou V.c · Constantoyannis C.a

Author affiliations

aFunctional Neurosurgery Unit, Department of Neurosurgery, bDepartment of Neurology, and cEndocrinology Unit, Department of Internal Medicine, University of Patras, Rion, Greece

Corresponding Author

Assist. Prof. Constantine Constantoyannis

Functional Neurosurgery Unit

Department of Neurosurgery, University Hospital of Patras

GR–26 500 Rion (Greece)

Tel. +30 69 4474 6083, E-Mail cconst@med.upatras.gr

Related Articles for ""

Stereotact Funct Neurosurg 2012;90:104–112

Do you have an account?

Login Information

Contact Information

By signing up for MyKarger you will automatically participate in our year-End raffle.
If you Then Do Not wish To participate, please uncheck the following box.

Yes, I wish To participate In the year-End raffle And Get the chance To win some Of our most interesting books, And other attractive prizes.

I have read the Karger Terms and Conditions and agree.


Background: The exact mechanism of weight gain (WG) after deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with idiopathic Parkinson’s disease remains unknown. Objectives: To investigate a possible involvement of ghrelin, neuropeptide Y (NPY) and leptin in WG after DBS. Methods: Twenty-three Parkinson patients were submitted for body composition measurements and blood sampling 3 days before, and 3 and 6 months after STN DBS. Peripheral concentrations of ghrelin, NPY, and leptin were determined, as well as the L-dopa equivalent daily dose. Patients were clinically evaluated using the Unified Parkinson’s Disease Rating Scale. Results: Three months after surgery, a significant WG was observed (3.09 ± 5.00 kg; p = 0.007) with no further increase at 6 months. Three months postoperatively, NPY circulating levels increased significantly (p = 0.05), while the increase of ghrelin levels reached statistical significance at 6 months (p = 0.001). WG was significantly associated with changes of ghrelin and leptin levels at 3 and 6 months, respectively. Conclusions: STN DBS seems to temporarily dysregulate the hypothalamic secretion of NPY and ghrelin. The variation of weight may be attributed to an increased production of ghrelin and leptin. A possible neuroprotective role of DBS, exerted through the increase of ghrelin levels, should be further studied.

© 2012 S. Karger AG, Basel


  1. Poewe W: Non motor symptoms in parkinson’s disease; in Jankovic J, Tolosa E (eds): Parkinson’s Disease and Movement Disorders, ed 5. Philadelphia, Lippincott Williams and Wilkins, 2007, pp 67–76.
  2. Markus HS, Cox M, Tomkins AM: Raised resting energy expenditure in parkinson’s disease and its relationship to muscle rigidity. Clin Sci (Lond) 1992;83:199–204.
  3. Jankovic J, Wooten M, Van der Linden C, Jansson B: Low body weight in parkinson’s disease. South Med J 1992;85:351–354.
  4. Beyer PL, Palarino MY, Michalek D, Busenbark K, Koller WC: Weight change and body composition in patients with parkinson’s disease. J Am Diet Assoc 1995;95:979–983.
  5. Perlemoine C, Macia F, Tison F, Coman I, Guehl D, Burbaud P, Cuny E, Baillet L, Gin H, Rigalleau V: Effects of subthalamic nucleus deep brain stimulation and levodopa on energy production rate and substrate oxidation in parkinson’s disease. Br J Nutr 2005;93:191–198.
  6. Gironell A, Pascual-Sedano B, Otermin P, Kulisevsky J: Weight gain after functional surgery for parkinsons disease. Neurologia 2002;17:310–316.
  7. Novakova L, Ruzicka E, Jech R, Serranova T, Dusek P, Urgosik D: Increase in body weight is a non-motor side effect of deep brain stimulation of the subthalamic nucleus in parkinson’s disease. Neuro Endocrinol Lett 2007;28:21–25.
    External Resources
  8. Montaurier C, Morio B, Bannier S, Derost P, Arnaud P, Brandolini-Bunlon M, Giraudet C, Boirie Y, Durif F: Mechanisms of body weight gain in patients with parkinson’s disease after subthalamic stimulation. Brain 2007;130:1808–1818.
  9. Macia F, Perlemoine C, Coman I, Guehl D, Burbaud P, Cuny E, Gin H, Rigalleau V, Tison F: Parkinson’s disease patients with bilateral subthalamic deep brain stimulation gain weight. Mov Disord 2004;19:206–212.
    External Resources
  10. Barichella M, Marczewska AM, Mariani C, Landi A, Vairo A, Pezzoli G: Body weight gain rate in patients with parkinson’s disease and deep brain stimulation. Mov Disord 2003;18:1337–1340.
    External Resources
  11. Vardi J, Oberman Z, Rabey I, Streifler M, Ayalon D, Herzberg M: Weight loss in patients treated long-term with levodopa. Metabolic aspects. J Neurol Sci 1976;30:33–40.
  12. Chen TY, Duh SL, Huang CC, Lin TB, Kuo DY: Evidence for the involvement of dopamine d(1) and d(2) receptors in mediating the decrease of food intake during repeated treatment with amphetamine. J Biomed Sci 2001;8:462–466.
  13. Kalra SP, Dube MG, Pu S, Xu B, Horvath TL, Kalra PS: Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocr Rev 1999;20:68–100.
  14. Murphy KG, Dhillo WS, Bloom SR: Gut peptides in the regulation of food intake and energy homeostasis. Endocr Rev 2006;27:719–727.
  15. Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, Dhillo WS, Ghatei MA, Bloom SR: Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 2001;86:5992.
  16. Druce M, Bloom SR: The regulation of appetite. Arch Dis Child 2006;91:183–187.
  17. Yamada T, Katagiri H: Avenues of communication between the brain and tissues/organs involved in energy homeostasis. Endocr J 2007;54:497–505.
  18. Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K, Matsukura S: A role for ghrelin in the central regulation of feeding. Nature 2001;409:194–198.
  19. Steiger A: Eating and sleeping – their relationship to ghrelin and leptin. Am J Physiol Regul Integr Comp Physiol 2004;287:R1031–R1032.
  20. Yildiz BO, Suchard MA, Wong ML, McCann SM, Licinio J: Alterations in the dynamics of circulating ghrelin, adiponectin, and leptin in human obesity. Proc Natl Acad Sci USA 2004;101:10434–10439.
  21. Toshinai K, Date Y, Murakami N, Shimada M, Mondal MS, Shimbara T, Guan JL, Wang QP, Funahashi H, Sakurai T, Shioda S, Matsukura S, Kangawa K, Nakazato M: Ghrelin-induced food intake is mediated via the orexin pathway. Endocrinology 2003;144:1506–1512.
  22. Valassi E, Scacchi M, Cavagnini F: Neuroendocrine control of food intake. Nutr Metab Cardiovasc Dis 2008;18:158–168.
  23. Gil-Campos M, Aguilera CM, Canete R, Gil A: Ghrelin: a hormone regulating food intake and energy homeostasis. Br J Nutr 2006;96:201–226.
  24. Stanley S, Wynne K, McGowan B, Bloom S: Hormonal regulation of food intake. Physiol Rev 2005;85:1131–1158.
  25. Escamilla-Sevilla F, Perez-Navarro MJ, Munoz-Pasadas M, Saez-Zea C, Jouma-Katati M, Piedrola-Maroto G, Ramirez-Navarro A, Minguez-Castellanos A: Change of the melanocortin system caused by bilateral subthalamic nucleus stimulation in parkinson’s disease. Acta Neurol Scand 2011;124:275–281.
  26. Bannier S, Montaurier C, Derost PP, Ulla M, Lemaire JJ, Boirie Y, Morio B, Durif F: Overweight after deep brain stimulation of the subthalamic nucleus in parkinson disease: long term follow-up. J Neurol Neurosurg Psychiatry 2009;80:484–488.
  27. Lukaski HC: Methods for the assessment of human body composition: traditional and new. Am J Clin Nutr 1987;46:537–556.
  28. Grosset K, Needleman F, Macphee G, Grosset D: Switching from ergot to nonergot dopamine agonists in parkinson’s disease: a clinical series and five-drug dose conversion table. Mov Disord 2004;19:1370–1374.
  29. Schaltenbrand G, Wahren A: Stereotaxic Atlas of the Human Brain. New York, Thieme Verlag, 1982.
  30. Guimaraes J, Matos E, Rosas MJ, Vieira-Coelho A, Borges N, Correia F, Vaz R, Garrett C: Modulation of nutritional state in Parkinsonian patients with bilateral subthalamic nucleus stimulation. J Neurol 2009;256:2072–2078.
  31. Abbott RA, Cox M, Markus H, Tomkins A: Diet, body size and micronutrient status in parkinson’s disease. Eur J Clin Nutr 1992;46:879–884.
  32. Bachmann CG, Trenkwalder C: Body weight in patients with parkinson’s disease. Mov Disord 2006;21:1824–1830.
    External Resources
  33. Nozaki S, Saito T, Matsumura T, Miyai I, Kang J: Relationship between weight loss and dysphagia in patients with parkinson’s disease. Rinsho Shinkeigaku 1999;39:1010–1014.
  34. McDonald WM, Richard IH, DeLong MR: Prevalence, etiology, and treatment of depression in parkinson’s disease. Biol Psychiatry 2003;54:363–375.
    External Resources
  35. Muller A, Mungersdorf M, Reichmann H, Strehle G, Hummel T: Olfactory function in parkinsonian syndromes. J Clin Neurosci 2002;9:521–524.
  36. Markus HS, Tomkins AM, Stern GM: Increased prevalence of undernutrition in parkinson’s disease and its relationship to clinical disease parameters. J Neural Transm Park Dis Dement Sect 1993;5:117–125.
  37. Tuite PJ, Maxwell RE, Ikramuddin S, Kotz CM, Billington CJ, Laseski MA, Thielen SD: Weight and body mass index in parkinson’s disease patients after deep brain stimulation surgery. Parkinsonism Relat Disord 2005;11:247–252.
    External Resources
  38. Corcuff JB, Krim E, Tison F, Foubert-Sanier A, Guehl D, Burbaud P, Cuny E, Baillet L, Gin H, Rigalleau V, Perlemoine C: Subthalamic nucleus stimulation in patients with parkinson’s disease does not increase serum ghrelin levels. Br J Nutr 2006;95:1028–1029.
  39. Andrews ZB, Erion D, Beiler R, Liu ZW, Abizaid A, Zigman J, Elsworth JD, Savitt JM, DiMarchi R, Tschoep M, Roth RH, Gao XB, Horvath TL: Ghrelin promotes and protects nigrostriatal dopamine function via a ucp2-dependent mitochondrial mechanism. J Neurosci 2009;29:14057–14065.
  40. Jiang H, Li LJ, Wang J, Xie JX: Ghrelin antagonizes MPTP-induced neurotoxicity to the dopaminergic neurons in mouse substantia nigra. Exp Neurol 2008;212:532–537.
  41. Czermak C, Hauger R, Drevets WC, Luckenbaugh DA, Geraci M, Charney DS, Neumeister A: Plasma NPY concentrations during tryptophan and sham depletion in medication-free patients with remitted depression. J Affect Disord 2008;110:277–281.
  42. Moon J, Tobkin S, Smith A, Roberts M, Ryan E, Dalbo V, Lockwood C, Walter A, Cramer J, Beck T, Stout J: Percent body fat estimations in college men using field and laboratory methods: a three-compartment model approach. Dyn Med 2008;7:7.
    External Resources

Article / Publication Details

First-Page Preview
Abstract of Clinical Study

Received: March 01, 2011
Accepted: November 14, 2011
Published online: March 02, 2012
Issue release date: April 2012

Number of Print Pages: 9
Number of Figures: 1
Number of Tables: 5

ISSN: 1011-6125 (Print)
eISSN: 1423-0372 (Online)

For additional information: https://www.karger.com/SFN

Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.