The Physiological Relationships Between the Brainstem, Vagal Stimulation, and Feeding



Food intake is controlled in the brain which integrates important regulatory information from the periphery, especially the gut. A large part of this gut-brain signaling is transmitted by the vagus nerve from the gastrointestinal tract to the brainstem. Mechanical as well as chemical information is sensed by vagal afferents through direct activation of mechano- and chemoreceptors triggered by peptides such as ghrelin, cholecystokinin, glucagon-like peptide-1, peptide YY and glucagon, or transmitters (serotonin) released from enteroendocrine cells. The activated vagus in turn stimulates cells in brainstem nuclei eliciting reflexes that influence feeding behavior, gut hormonet, and gastric functions such as motility as well as secretion and are involved in glucose homeostasis. Therefore, the brainstem and the vagus are actively involved in food intake and digestive processes. Obesity and associated diseases are major health problems in the industrialized countries and curative measures are limited. The most effective treatment is bariatric surgery that bypasses the stomach and may involve a vagal component underlying the sustained weight loss. Besides surgery, drugs, and cognitive approaches, gastric electrical stimulation has also been shown to induce long-lasting weight loss. However, further studies are needed to unravel the role of the vagus nerve for weight loss after those procedures and optimizing therapeutic strategies.


Bariatric Surgery Vagus Nerve Ghrelin Level Gastric Electrical Stimulation Enteroendocrine Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Body mass index


Cocaine- and amphetamine-regulated transcript




Dorsal motor nucleus of the vagus nerve


1/2 extracellular signal-regulated kinase 1/2


Gastric electrical stimulation

GHS-R 1a

Growth hormone secretagogue receptor type 1a


Glucagon-like peptide-1








Melanin-concentrating hormone


Melanin-concentrating hormone receptor 1




Nitric oxide


Nucleus of the solitary tract


Peptide YY


Roux-en-Y gastric bypass


Substance P


Thyrotropin-releasing hormone

Ucn 2

Urocortin 2



Y.T. is in receipt of VA Research Career Scientist Award and R01 NIHDDK grants (DK 57238 and 33061). A.S. is supported by the German Research Foundation Grant STE 1765/1–1.


  1. Abell TL, Minocha A, Abidi N Am J Med Sci. 2006;331:226–32.PubMedCrossRefGoogle Scholar
  2. Ao Y, Go VL, Toy N, Li T, Wang Y, Song MK, Reeve JR Jr, Liu Y, Yang H Endocrinology. 2006;147:6004–10.PubMedCrossRefGoogle Scholar
  3. Arnold M, Mura A, Langhans W, Geary N J Neurosci. 2006;26:11052–60.PubMedCrossRefGoogle Scholar
  4. Bado A, Levasseur S, Attoub S, Kermorgant S, Laigneau JP, Bortoluzzi MN, Moizo L, Lehy T, Guerre-Millo M, Le Marchand-Brustel Y, Lewin MJ Nature. 1998;394:790–93.PubMedCrossRefGoogle Scholar
  5. Balsiger BM, Kennedy FP, Abu-Lebdeh HS, Collazo-Clavell M, Jensen MD, O’Brien T, Hensrud DD, Dinneen SF, Thompson GB, Que FG, Williams DE, Clark MM, Grant JE, Frick MS, Mueller RA, Mai JL, Sarr MG Mayo Clin Proc. 2000;75:673–80.PubMedCrossRefGoogle Scholar
  6. Barrachina MD, Martinez V, Wang L, Wei JY, Taché Y Proc Natl Acad Sci USA. 1997;94:10455–60.PubMedCrossRefGoogle Scholar
  7. Batterham RL, Cowley MA, Small CJ, Herzog H, Cohen MA, Dakin CL, Wren AM, Brynes AE, Low MJ, Ghatei MA, Cone RD, Bloom SR Nature. 2002;418:650–54.PubMedCrossRefGoogle Scholar
  8. Berthoud HR, Kressel M, Raybould HE, Neuhuber WL Anat Embryol (Berl). 1995;191:203–212.CrossRefGoogle Scholar
  9. Berthoud HR. Regul Pept. 2008;149:15–25.PubMedCrossRefGoogle Scholar
  10. Bohdjalian A, Prager G, Aviv R, Policker S, Schindler K, Kretschmer S, Riener R, Zacherl J, Ludvik B Obes Surg. 2006;16:627–34.PubMedCrossRefGoogle Scholar
  11. Bordi C, D’Adda T, Azzoni C, Ferraro G Microsc Res Tech. 2000;48:258–71.PubMedCrossRefGoogle Scholar
  12. Bucinskaite V, Tolessa T, Pedersen J, Rydqvist B, Zerihun L, Holst JJ, Hellstrom, PM. Neurogastroenterol Motil. 2009;21:978–e78.Google Scholar
  13. Burdyga G, Varro A, Dimaline R, Thompson DG, Dockray GJ Am J Physiol Gastrointest Liver Physiol. 2006;290:G1289–G1297.PubMedCrossRefGoogle Scholar
  14. Burdyga G, de Lartigue G, Raybould HE, Morris R, Dimaline R, Varro A, Thompson DG, Dockray GJ J Neurosci. 2008;28:11583–592.PubMedCrossRefGoogle Scholar
  15. Buyse M, Ovesjo ML, Goiot H, Guilmeau S, Peranzi G, Moizo L, Walker F, Lewin, MJ, Meister B, Bado A Eur J Neurosci. 2001;14:64–72.PubMedCrossRefGoogle Scholar
  16. Chaudhri OB, Salem V, Murphy KG, Bloom SR Annu Rev Physiol. 2008;70:239–55.PubMedCrossRefGoogle Scholar
  17. Chelikani PK, Haver AC, Reidelberger RD Am J Physiol Regul Integr Comp Physiol. 2005;288:R1695–706.PubMedCrossRefGoogle Scholar
  18. Chelikani PK, Haver AC, Reeve JR Jr, Keire DA, Reidelberger RD Am J Physiol Regul Integr Comp Physiol. 2006;290:R298–305.PubMedCrossRefGoogle Scholar
  19. Cigaina V. Obes Surg. 2002;12(Suppl 1):12S–16S.PubMedCrossRefGoogle Scholar
  20. Cigaina VV, Saggioro A, Rigo VV, Pinato G, Ischai S Obes Surg. 1996;6:250–53.PubMedCrossRefGoogle Scholar
  21. Cummings DE, Purnell JQ, Frayo RS, Schmidova K, Wisse BE, Weigle DS Diabetes 2001;50:1714–19.PubMedCrossRefGoogle Scholar
  22. Cummings DE, Weigle DS, Frayo RS, Breenc PA, Ma MK, Dellinger EP, Purnell JQ N Engl J Med. 2002;346:1623–30.PubMedCrossRefGoogle Scholar
  23. Cummings DE, Overduin J J Clin Invest. 2007;117:13–23.PubMedCrossRefGoogle Scholar
  24. Date Y, Kojima M, Hosoda H, Sawaguchi A, Mondal MS, Suganuma T, Matsukura S, Kangawa K, Nakazato M Endocrinology. 2000;141:4255–61.PubMedCrossRefGoogle Scholar
  25. Date Y, Murakami N, Toshinai K, Matsukura S, Niijima A, Matsuo H, Kangawa K, Nakazato M Gastroenterology 2002a;123:1120–28.PubMedCrossRefGoogle Scholar
  26. Date Y, Nakazato M, Hashiguchi S, Dezaki K, Mondal MS, Hosoda H, Kojima M, Kangawa K, Arima T, Matsuo H, Yada T, Matsukura S Diabetes 2002b;51:124–9.PubMedCrossRefGoogle Scholar
  27. De Luca M, Segato G, Busetto L, Favretti F, Aigner F, Weiss H, de Gheldere C, Gaggiotti G, Himpens J, Limao J, Scheyer M, Toppino M, Zurmeyer EL, Bottani G, Penthaler H Obes Surg. 2004;14(Suppl 1):S33–9.PubMedCrossRefGoogle Scholar
  28. Desai KM, Zembowicz A, Sessa WC, Vane JR Proc Natl Acad Sci USA. 1991;88:11490–94.PubMedCrossRefGoogle Scholar
  29. Dockray G. Curr Opin Pharmacol. 2004;4:557–60.PubMedCrossRefGoogle Scholar
  30. Dockray GJ. Physiol Behav. 2009;97:531–6.PubMedCrossRefGoogle Scholar
  31. Flegal KM, Carroll MD, Kuczmarski RJ, Johnson CL Int J Obes Relat Metab Disord. 1998;22:39–47.PubMedCrossRefGoogle Scholar
  32. Flegal KM, Graubard BI, Williamson DF, Gail MH JAMA. 2007;298:2028–37.PubMedCrossRefGoogle Scholar
  33. Friedman JM, Halaas JL Nature. 1998;395:763–70.PubMedCrossRefGoogle Scholar
  34. Gourcerol G, Wang L, Wang YH, Million M, Taché Y Endocrinology. 2007;148:6115–623.PubMedCrossRefGoogle Scholar
  35. Goyal RK, Rattan S, Said SI Nature. 1980;288:378–80.PubMedCrossRefGoogle Scholar
  36. Grill HJ, Kaplan JM Front Neuroendocrinol. 2002;23:2–40.PubMedCrossRefGoogle Scholar
  37. Gura T. Science. 2003;299:849–52.PubMedCrossRefGoogle Scholar
  38. Gutzwiller JP, Degen L, Matzinger D, Prestin S, Beglinger C Am J Physiol Regul Integr Comp Physiol. 2004;287:R562–7.PubMedCrossRefGoogle Scholar
  39. Hasler WL. Neurogastroenterol Motil. 2009;21:229–43.PubMedCrossRefGoogle Scholar
  40. Hoeller E, Aigner F, Margreiter R, Weiss H Obes Surg. 2006;16:1160–65.PubMedCrossRefGoogle Scholar
  41. James WP. J Intern Med. 2008;263:336–52.PubMedCrossRefGoogle Scholar
  42. Kakei M, Yada T, Nakagawa A, Nakabayashi H Auton Neurosci. 2002;102:39–44.PubMedCrossRefGoogle Scholar
  43. Kalia M, Fuxe K, Goldstein M, Harfstrand A, Agnati LF, Coyle JT Neurosci Lett. 1984;50:57–62.PubMedCrossRefGoogle Scholar
  44. Keire DA, Bowers CW, Solomon TE, Reeve JR Jr Peptides. 2002;23:305–21.PubMedCrossRefGoogle Scholar
  45. Kobelt P, Tebbe JJ, Tjandra I, Stengel A, Bae HG, Andresen V, van der Voort IR, Veh RW, Werner CR, Klapp BF, Wiedenmann B, Wang L, Taché Y, Mönnikes H Am J Physiol Regul Integr Comp Physiol. 2005;288:R751–8.PubMedCrossRefGoogle Scholar
  46. Kobelt P, Goebel M, Stengel A, Schmidtmann M, van der Voort IR, Tebbe JJ, Veh RW, Klapp BF, Wiedenmann B, Wang L, Taché Y, Mönnikes H Am J Physiol Regul Integr Comp Physiol. 2006;291:R903–913.PubMedCrossRefGoogle Scholar
  47. Koda S, Date Y, Murakami N, Shimbara T, Hanada T, Toshinai K, Niijima A, Furuya M, Inomata N, Osuye K, Nakazato M Endocrinology. 2005;146:2369–75.PubMedCrossRefGoogle Scholar
  48. Krowicki ZK, Sharkey KA, Serron SC, Nathan NA, Hornby PJ J Comp Neurol. 1997;377:49–69.PubMedCrossRefGoogle Scholar
  49. Le Roux CW, Neary NM, Halsey TJ, Small CJ, Martinez-Isla AM, Ghatei MA, Theodorou NA, Bloom SR J Clin Endocrinol Metab. 2005;90:4521–4.PubMedCrossRefGoogle Scholar
  50. Maier C, Schaller G, Buranyi B, Nowotny P, Geyer G, Wolzt M, Luger A J Clin Endocrinol Metab. 2004;89:4729–33.PubMedCrossRefGoogle Scholar
  51. Marx J. Science. 2003;299:846–9.PubMedCrossRefGoogle Scholar
  52. Miampamba M, Yang H, Sharkey KA, Taché Y Am J Physiol Gastrointest Liver Physiol. 2001;280:G979–91.PubMedGoogle Scholar
  53. Moran TH. Obesity (Silver Spring). 2006;14(Suppl 5):250S–53S.CrossRefGoogle Scholar
  54. Morrison SF. Clin Exp Pharmacol Physiol. 2001;28:138–43.CrossRefGoogle Scholar
  55. Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM JAMA. 2006;295:1549–55.PubMedCrossRefGoogle Scholar
  56. Peles S, Petersen J, Aviv R, Policker S, Abu-Hatoum O, Ben-Haim SA, Gutterman DD, Sengupta JN Am J Physiol Gastrointest Liver Physiol. 2003;285:G577–85.PubMedGoogle Scholar
  57. Phillips RJ, Powley TL Brain Res Brain Res Rev. 2000;34:1–26.PubMedCrossRefGoogle Scholar
  58. Powley TL, Chi MM, Schier LA, Phillips RJ Physiol Behav. 2005;86:698–708.PubMedCrossRefGoogle Scholar
  59. Rinaman L, Hoffman GE, Dohanics J, Le WW, Stricker EM, Verbalis JG J Comp Neurol. 1995;360:246–56.PubMedCrossRefGoogle Scholar
  60. Rüttimann EB, Arnold M, Hillebrand JJ, Geary N, Langhans W Endocrinology. 2009;150:1174–81.PubMedCrossRefGoogle Scholar
  61. Schemann M, Grundy D Am J Physiol. 1992;263:G709–718.PubMedGoogle Scholar
  62. Schwartz GJ. Phil Trans R Soc Lond B Biol Sci. 2006;361:1275–80.CrossRefGoogle Scholar
  63. Shi H, Bartness TJ Brain Res Bull. 2001;54:375–85.PubMedCrossRefGoogle Scholar
  64. Shikora SA. Obes Surg. 2004;14(Suppl 1):S40–48.PubMedCrossRefGoogle Scholar
  65. Shimazu T. Biochim Biophys Acta. 1971;252:28–38.CrossRefGoogle Scholar
  66. Simonian HP, Kresge KM, Boden GH, Parkman HP Neurogastroenterol Motil. 2005;17:348–54.PubMedCrossRefGoogle Scholar
  67. Sjostrom L, Lindroos AK, Peltonen M, Torgerson J, Bouchard C, Carlsson B, Dahlgren S, Larsson B, Narbro K, Sjostrom CD, Sullivan M, Wedel H N Engl J Med. 2004;351:2683–93.PubMedCrossRefGoogle Scholar
  68. Sugerman HJ, Wolfe LG, Sica DA, Clore JN Ann Surg. 2003;237:751–58.PubMedGoogle Scholar
  69. Sutton GM, Patterson LM, Berthoud HR J Neurosci. 2004;24:10240–47.PubMedCrossRefGoogle Scholar
  70. Taché Y, Yang H, Miampamba M, Martinez V, Yuan PQ Auton Neurosci. 2006;125:42–52.PubMedCrossRefGoogle Scholar
  71. Taché Y. In: Zafra MA, Molina F, Puerto A, edidors. The cephalic/neural phase in nutrition. Research Signpost. 2009; pp. 47–58.Google Scholar
  72. Tanner BD, Allen JW Am Surg. 2009;75:103–112.PubMedGoogle Scholar
  73. Travagli RA, Hermann GE, Browning KN, Rogers RC Annu Rev Physiol. 2006;68:279–305.PubMedCrossRefGoogle Scholar
  74. Van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, Schrauwen P, Teule GJ N Engl J Med. 2009;360:1500–508.PubMedCrossRefGoogle Scholar
  75. Wang L, Barachina MD, Martinez V, Wei JY, Taché Y Regul Pept. 2000;92:79–85.PubMedCrossRefGoogle Scholar
  76. Wang YH, Taché Y, Sheibel AB, Go VL, Wei JY Am J Physiol. 1997;273:R833–7.PubMedGoogle Scholar
  77. Waters GS, Pories WJ, Swanson MS, Meelheim HD, Flickinger EG, May HJ Am J Surg. 1991;161:154–7.PubMedCrossRefGoogle Scholar
  78. Woods SC, Lutz TA, Geary N, Langhans W Phil Trans R Soc Lond B Biol Sci. 2006;361:1219–35.CrossRefGoogle Scholar
  79. Wren AM, Bloom SR Gastroenterology. 2007;132:2116–30.PubMedCrossRefGoogle Scholar
  80. Wynne K, Stanley S, Bloom S J Clin Endocrinol Metab. 2004;89:2576–82.PubMedCrossRefGoogle Scholar
  81. Yale CE. Arch Surg. 1989;124:941–6.PubMedCrossRefGoogle Scholar
  82. Zhang J, Chen JD Aliment Pharmacol Ther. 2006;24:991–1002.PubMedCrossRefGoogle Scholar
  83. Zhang J, Tang M, Chen JD Obesity (Silver Spring). 2009;17:474–80.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.CURE: Digestive Diseases Research Center, David Geffen School of MedicineUniversity of California, Los AngelesLos AngelesUSA

Personalised recommendations