Brief Report| Volume 64, ISSUE 11, P1005-1008, December 01, 2008

Deranged Secretion of Ghrelin and Obestatin in the Cephalic Phase of Vagal Stimulation in Women with Anorexia Nervosa


      Vagal activation in the cephalic phase response to food ingestion promotes ghrelin secretion. Because underweight individuals with anorexia nervosa (AN) are characterized by increased vagal tone, we hypothesized an enhanced ghrelin production in the cephalic phase of vagal stimulation. Therefore, we investigated the responses of ghrelin and its recently discovered sibling peptide obestatin to modified sham feeding (MSF) in both AN and healthy women.


      Eight AN women and eight age-matched healthy female subjects underwent MSF, with initially seeing and smelling a meal and then chewing the food without swallowing it. Blood samples were drawn before and after MSF for hormone assays.


      Circulating ghrelin increased, whereas obestatin decreased after MSF. Compared with healthy women, AN individuals exhibited enhanced ghrelin and obestatin baseline plasma levels and amplified MSF-induced ghrelin increase and obestatin drop. Ghrelin secretion positively correlated with subjects' eating behavior as assessed by the Three-Factor Eating Questionnaire.


      Opposite changes in circulating ghrelin and obestatin occur in the cephalic phase of vagal stimulation, and these changes are amplified in symptomatic AN patients. Given the opposite effects of ghrelin and obestatin on food intake, these findings may have pathophysiologic implications for the dysregulated eating behavior of AN individuals.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Taylor I.L.
        • Feldman M.
        • Richardson C.T.
        • Walsh J.H.
        Gastric and cephalic stimulation of human pancreatic polypeptide release.
        Gastroenterology. 1978; 75: 432-437
        • Feldman M.
        • Richardson C.T.
        Role of thought, sight, smell, and taste of food in the cephalic phase of gastric acid secretion in humans.
        Gastroenterology. 1986; 90: 428-433
        • Robertson M.D.
        • Jackson K.G.
        • Williams C.M.
        • Fielding B.A.
        • Frayn K.N.
        Prolonged effects of modified sham feeding on energy substrate mobilization.
        Am J Clin Nutr. 2001; 73: 111-117
        • Simonian H.P.
        • Kresge K.M.
        • Boden G.H.
        • Parkman H.P.
        Differential effects of sham feeding and meal ingestion on ghrelin and pancreatic polypeptide levels: evidence for vagal efferent stimulation mediating ghrelin release.
        Neurogastroenterol Motil. 2005; 17: 348-354
        • Favaro A.
        • Monteleone P.
        • Santonastaso P.
        • Maj M.
        Psychobiology of eating disorders.
        in: Wonderlich S. Mitchell J.E. de Zwann M. Steiger H. Annual Review of Eating Disorders. Radcliffe, New York2008: 9-34 (Part 2—2008)
        • Kollai M.
        • Bonyhay I.
        • Jokkel G.
        • Szonyi L.
        Cardiac vagal hyperactivity in adolescent anorexia nervosa.
        Eur Heart J. 1994; 15: 1113-1118
        • Rechlin T.
        • Weis M.
        • Ott C.
        • Bleichner F.
        • Joraschky P.
        Alterations of autonomic cardiac control in anorexia nervosa.
        Biol Psychiatry. 1998; 43: 358-363
        • Galetta F.
        • Franzoni F.
        • Prattichizzo F.
        • Rolla M.
        • Santoro G.
        • Pentimone F.
        Heart rate variability and left ventricular diastolic function in anorexia nervosa.
        J Adolesc Health. 2003; 32: 416-421
        • Zhang J.V.
        • Ren P.G.
        • Avsian-Kretchmer O.
        • Luo C.W.
        • Rauch R.
        • Klein C.
        • et al.
        Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake.
        Science. 2005; 310: 996-999
        • First M.B.
        • Spitzer R.L.
        • Gibbon M.
        • Williams J.B.
        Structured Clinical Interview for DSM-IV Axis I Disorders—Patient Edition.
        (SCID-I/P, Version 2) New York State Psychiatric Institute, Biometrics Research Department, New York1995
        • First M.B.
        • Gibbon M.
        • Spitzer R.L.
        • Williams J.B.W.
        Structured Clinical Interview for Axis I DSM-IV Disorders—Nonpatient Edition.
        (SCID-I/NP, Version 2.0) New York State Psychiatric Institute, Biometrics Research Department, New York1996
        • Andreasen N.C.
        • Endicott J.
        • Spitzer R.L.
        • Winokur G.
        The family history method using diagnostic criteria: Reliability and validity.
        Arch Gen Psychiatry. 1997; 34: 1229-1235
        • Stunkard A.J.
        • Messick S.
        The three-factor eating questionnaire to measure dietary restraint, disinhibition and hunger.
        J Psychosom Res. 1985; 29: 71-83
        • Dixon J.
        BMDP Statistical Software.
        University of California Press, Berkley1985
        • Arosio M.
        • Ronchi C.L.
        • Beck-Peccoz P.
        • Gebbia C.
        • Ciavoli C.
        • Cappiello V.
        • et al.
        Effects of modified sham feeding on ghrelin levels in healthy human subjects.
        J Clin Endocrinol Metab. 2004; 89: 5101-5104
        • Seoane L.M.
        • Al-Massadi O.
        • Pazos Y.
        • Fagotto U.
        • Casanueva F.F.
        Central obestatin administration does not modify either spontaneous or ghrelin-induced food intake in rats.
        J Endocrinol Invest. 2006; 29: RC13-RC15
        • Zizzari P.
        • Longshamps R.
        • Epelbaum J.
        • Bluet-Pajot M.T.
        Obestatin partially affect ghrelin stimulation of food intake and growth hormone secretion in rodents.
        Endocrinology. 2007; 148: 1648-1653
        • Harada T.
        • Nakahara T.
        • Yasuhara D.
        • Kojima S.
        • Sagiyama K.-I.
        • Amitani H.
        • et al.
        Obestatin, acylghrelin, and des-acylghrelin responses to an oral glucose tolerance test in the restricting type of anorexia nervosa.
        Biol Psychiatry. 2008; 63: 245-247
        • Nakahara T.
        • Harada T.
        • Yasuhara D.
        • Shimada N.
        • Amitani H.
        • Sakoguchi T.
        • et al.
        Plasma obestatin concentrations are negatively correlated with body mass index, insulin resistance index, and plasma leptin concentrations in obesity and anorexia nervosa.
        Biol Psychiatry. 2007; ([published online ahead of print October 3])