, Volume 221, Issue 4, pp 693–700 | Cite as

Sibutramine promotes amygdala activity under fasting conditions in obese women

  • Kerstin M. OltmannsEmail author
  • Marcus Heldmann
  • Susanne Daul
  • Silke Klose
  • Michael Rotte
  • Michael Schäfer
  • Hans-Jochen Heinze
  • Thomas F. Münte
  • Hendrik Lehnert
Original Investigation



Sibutramine, a centrally-acting selective monoamine reuptake inhibitor, has been used as an appetite suppressant drug in obesity.


To gain insight into the central nervous actions of sibutramine, brain responses to pictures of food items after sibutramine vs placebo application were assessed by functional magnetic resonance imaging (fMRI) in obese women.


In a randomized double-blind crossover design, 10 healthy obese women (BMI 31.8–39.9 kg/m2) received 15 mg/d of sibutramine vs placebo for 14 d. Obese participants, and a group of 10 age-matched normal weight controls, viewed pictures of food items and control objects in hungry and satiated states while lying in the MR scanner. The paradigm followed a block design. In obese participants, fMRI measurements were conducted prior and after two weeks of daily sibutramine or placebo administration, whereas control participants were scanned only at one point in time.


Upon food item presentation, obese participants showed increased brain activity in areas related to emotional and reward processing, perceptual processing, and cognitive control as compared to normal weight controls. Sibutramine exerted a divergent satiety-dependent effect on amygdala activity in obese participants, increasing activity in the hungry state while decreasing it under conditions of satiation.


Our results demonstrate a modulatory influence of sibutramine on amygdala activity in obese women which may underlie the appetite suppressant effects of the drug.


Obesity Appetite Body weight fMRI Reward Satiety Hunger Weight loss 



The study was supported by an unrestricted educational grant by Abbott GmbH & Co. KG, Germany. KMO, TFM, and HL were supported by grants of the German Research Foundation (DFG) and the Federal Ministry of Education and Research (BMBF). The funding source had no role in design, analyses, interpretation, or publication of this article.


  1. Baranowska B, Wolinska-Witort E, Martynska L, Chmielowska M, Mazurczak-Pluta T, Boguradzka A, Baranowska-Bik A (2005) Sibutramine therapy in obese women—effects on plasma neuropeptide Y, NPY, insulin, leptin and beta-endorphin concentrations. Neuroendocrinol Lett 26:675–679PubMedGoogle Scholar
  2. Berthoud HR, Morrison C (2008) The brain, appetite, and obesity. Annu Rev Psychol 59:55–92PubMedCrossRefGoogle Scholar
  3. Born JM, Lemmens SG, Martens MJ, Formisano E, Goebel R, Westerterp-Plantenga MS (2011) Differences between liking and wanting signals in the human brain and relations with cognitive dietary restraint and body mass index. Am J Clin Nutr 94:392–403PubMedCrossRefGoogle Scholar
  4. Chapelot D, Marmonier C, Thomas F, Hanotin C (2000) Modalities of the food intake-reducing effect of sibutramine in humans. Physiol Behav 68:299–308PubMedCrossRefGoogle Scholar
  5. Curfman GD, Morrissey S, Drazen JM (2010) Sibutramine—another flawed diet pill. N Engl J Med 363:972–974PubMedCrossRefGoogle Scholar
  6. Del Parigi A, Chen K, Salbe AD, Reiman EM, Tataranni PA (2005) Sensory experience of food and obesity: a positron emission tomography study of the brain regions affected by tasting a liquid meal after a prolonged fast. NeuroImage 24:436–443CrossRefGoogle Scholar
  7. Del Parigi A, Chen K, Salbe AD, Hill JO, Wing RR, Reiman EM, Tataranni PA (2004) Persistence of abnormal neural responses to a meal in post obese individuals. Int J Obes Relat Metab Disord 28:370–377CrossRefGoogle Scholar
  8. Demos KE, Kelley WM, Heatherton TF (2011) Dietary restraint violations influence reward responses in nucleus accumbens and amygdala. J Cogn Neurosci 23:1952–63PubMedCrossRefGoogle Scholar
  9. Finer N (2002) Sibutramine: its mode of action and efficacy. Int J Obes Relat Metab Disord 26(Suppl 4):S29–S33PubMedCrossRefGoogle Scholar
  10. Fletcher PC, Napolitano A, Skeggs A, Miller SR, Delafont B, Cambridge VC, Nathan PJ, Brooke A, O’Rahilly S, Farooqi IS, Bullmore ET (2010) Distinct modulatory effects of satiety and sibutramine on brain responses to food images in humans: a double dissociation across hypothalamus, amygdala, and ventral striatum. J Neurosci 30:14346–14355PubMedCrossRefGoogle Scholar
  11. Gautier JF, Del Parigi A, Chen K, Salbe AD, Bandy D, Pratley RE, Ravussin E, Reiman EM, Tataranni PA (2001) Effect of satiation on brain activity in obese and lean women. Obes Res 9:676–684PubMedCrossRefGoogle Scholar
  12. Glascher J (2009) Visualization of group inference data in functional neuroimaging. Neuroinformatics 7:73–82PubMedCrossRefGoogle Scholar
  13. Goldstone AP, de Hernandez CG, Beaver JD, Muhammed K, Croese C, Bell G, Durighel G, Hughes E, Waldman AD, Frost G, Bell JD (2009) Fasting biases brain reward systems towards high-calorie foods. Eur J Neurosci 30:1625–1635PubMedCrossRefGoogle Scholar
  14. Heusser K, Engeli S, Tank J, Diedrich A, Wiesner S, Janke J, Luft FC, Jordan J (2007) Sympathetic vasomotor tone determines blood pressure response to long-term sibutramine treatment. J Clin Endocrinol Metab 92:1560–1563PubMedCrossRefGoogle Scholar
  15. James WP, Astrup A, Finer N, Hilsted J, Kopelman P, Rossner S, Saris WH, Van Gaal LF (2000) Effect of sibutramine on weight maintenance after weight loss: a randomised trial. STORM Study Group. Sibutramine Trial of Obesity Reduction and Maintenance. Lancet 356:2119–2125PubMedCrossRefGoogle Scholar
  16. James WP, Caterson ID, Coutinho W, Finer N, Van Gaal LF, Maggioni AP, Torp-Pedersen C, Sharma AM, Shepherd GM, Rode RA, Renz CL (2010) Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N Engl J Med 363:905–917PubMedCrossRefGoogle Scholar
  17. Kelley AE (2004) Ventral striatal control of appetitive motivation: role in ingestive behavior and reward-related learning. Neurosci Biobehav Rev 27:765–776PubMedCrossRefGoogle Scholar
  18. Killgore WD, Young AD, Femia LA, Bogorodzki P, Rogowska J, Yurgelun-Todd DA (2003) Cortical and limbic activation during viewing of high- versus low-calorie foods. NeuroImage 19:1381–1394PubMedCrossRefGoogle Scholar
  19. Killgore WD, Yurgelun-Todd DA (2006) Affect modulates appetite-related brain activity to images of food. Int J Eat Disord 39:357–363PubMedCrossRefGoogle Scholar
  20. LaBar KS, Gitelman DR, Parrish TB, Kim YH, Nobre AC, Mesulam MM (2001) Hunger selectively modulates corticolimbic activation to food stimuli in humans. Behav Neurosci 115:493–500PubMedCrossRefGoogle Scholar
  21. Lean ME (2001) How does sibutramine work? Int J Obes Relat Metab Disord 25(Suppl 4):S8–11PubMedCrossRefGoogle Scholar
  22. McNeely W, Goa KL (1998) Sibutramine: a review of its contribution to the management of obesity. Drugs 56:1093–1124PubMedCrossRefGoogle Scholar
  23. McNulty SJ, Ur E, Williams G (2003) A randomized trial of sibutramine in the management of obese type 2 diabetic patients treated with metformin. Diabetes Care 26:125–131PubMedCrossRefGoogle Scholar
  24. Passamonti L, Rowe JB, Schwarzbauer C, Ewbank MP, Calder AJ (2009) Personality predicts the brain’s response to viewing appetizing foods: the neural basis of a risk factor for overeating. J Neurosci 29:43–51PubMedCrossRefGoogle Scholar
  25. Pudel V, Westenhoefer J (1989) Fragebogen zum Eßverhalten. Handanweisung, Göttingen, HogreveGoogle Scholar
  26. Rolls BJ, Shide DJ, Thorwart ML, Ulbrecht JS (1998) Sibutramine reduces food intake in non-dieting women with obesity. Obes Res 6:1–11PubMedGoogle Scholar
  27. Siep N, Roefs A, Roebroeck A, Havermans R, Bonte ML, Jansen A (2009) Hunger is the best spice: an fMRI study of the effects of attention, hunger and calorie content on food reward processing in the amygdala and orbitofrontal cortex. Behav Brain Res 198:149–58PubMedCrossRefGoogle Scholar
  28. Stoeckel LE, Kim J, Weller RE, Cox JE, Cook EW III, Horwitz B (2009) Effective connectivity of a reward network in obese women. Brain Res Bull 79:388–395PubMedCrossRefGoogle Scholar
  29. Stoeckel LE, Weller RE, Cook EW III, Twieg DB, Knowlton RC, Cox JE (2008) Widespread reward-system activation in obese women in response to pictures of high-calorie foods. NeuroImage 41:636–647PubMedCrossRefGoogle Scholar
  30. Tataranni PA, Gautier JF, Chen K, Uecker A, Bandy D, Salbe AD, Pratley RE, Lawson M, Reiman EM, Ravussin E (1999) Neuroanatomical correlates of hunger and satiation in humans using positron emission tomography. Proc Natl Acad Sci USA 96:4569–4574PubMedCrossRefGoogle Scholar
  31. Tzourio-Mazoyer N, Landeau B, Papathanassiou D, Crivello F, Etard O, Delcroix N, Mazoyer B, Joliot M (2002) Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. NeuroImage 15:273–289PubMedCrossRefGoogle Scholar
  32. Wright CI, Beijer AV, Groenewegen HJ (1996) Basal amygdaloid complex afferents to the rat nucleus accumbens are compartmentally organized. J Neurosci 16:1877–1893PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Kerstin M. Oltmanns
    • 1
    Email author
  • Marcus Heldmann
    • 3
  • Susanne Daul
    • 4
  • Silke Klose
    • 4
  • Michael Rotte
    • 5
  • Michael Schäfer
    • 5
  • Hans-Jochen Heinze
    • 5
  • Thomas F. Münte
    • 3
  • Hendrik Lehnert
    • 2
  1. 1.Department of Psychiatry and PsychotherapyUniversity of LuebeckLuebeckGermany
  2. 2.Department of Internal Medicine IUniversity of LuebeckLuebeckGermany
  3. 3.Department of NeurologyUniversity of LuebeckLuebeckGermany
  4. 4.Division of Endocrinology and MetabolismMagdeburg University Medical School, Otto von Guericke University MagdeburgMagdeburgGermany
  5. 5.Department of NeurologyMagdeburg University Medical School, Otto von Guericke University MagdeburgMagdeburgGermany

Personalised recommendations