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This version published online on June 21, 2005
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2004-1874
A more recent version of this article appeared on September 1, 2005
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Submitted on September 23, 2004
Accepted on June 14, 2005

Is There A Role For Ghrelin And Peptide-YY In The Pathogenesis Of Obesity In Adults With Acquired Structural Hypothalamic Damage?

Christina Daousi*, Ian A. MacFarlane, Patrick J. English, John P.H. Wilding, Michael Patterson, Terence M. Dovey, Jason C.G. Halford, Mohammad A. Ghatei, and Jonathan H. Pinkney

Diabetes & Endocrinology Research Group, University Hospital Aintree, Clinical Sciences Center, Longmoor Lane, Liverpool L9 7AL, United Kingdom.; Department of Diabetes & Endocrinology, Derriford Hospital, Plymouth, United Kingdom.; Department of Metabolic Medicine, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom; Kissilef Laboratory, Department of Psychology, University of Liverpool, United Kingdom

* To whom correspondence should be addressed. E-mail: c.daousi{at}ntlworld.com.

Context: Obesity is a common sequel to hypothalamic tumors and their treatment but the underlying mechanisms are not fully established

Objective: to evaluate the role of ghrelin and peptide-YY (PYY) in human hypothalamic obesity

Setting: University Medical Center

Participants: 14 adult patients (6 male, 8 female) with tumors of the hypothalamic region and 15 healthy controls (6 male and 9 female) matched for age, body mass index and percentage body fat.

Interventions: Plasma ghrelin and total PYY were measured using RIAs after an overnight fast and 15, 30, 60, 120 and 180 min following a mixed meal.

Main outcome measures: ghrelin, PYY and appetite ratings

Results: The fall in ghrelin levels after the test meal was similar in the two groups. There was no statistically significant change postprandially in circulating PYY in the patients with hypothalamic damage. Fasting leptin levels and postprandial insulin responses were also similar in the two groups. Patients with hypothalamic damage reported higher hunger ratings at three hours post-meal (P = 0.01) and a stronger desire to eat at two (P = 0.01) and three hours (P = 0.02) compared with the control group.

Conclusions: Adult patients with structural hypothalamic damage show impaired satiety but the changes observed in circulating ghrelin and PYY concentrations in response to a test meal do not indicate a central role for these gut hormones in the control of appetite and the pathogenesis of obesity in these patients.
Key words: obesity • hypothalamus • ghrelin • PYY • appetite




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