International Journal of Obesity (2005) 29, 1130–1136

& 2005 Nature Publishing Group All rights reserved 0307-0565/05 $30.00
www.nature.com/ijo

PAPER
Ghrelin increases food intake in obese as well as lean
subjects
MR Druce1, AM Wren1, AJ Park1, JE Milton1, M Patterson1, G Frost1, MA Ghatei1, C Small1 and
SR Bloom1*
1
Department of Metabolic Medicine, Imperial College, London, Hammersmith Hospital Campus, London, UK

OBJECTIVE: To investigate whether effects on food intake are seen in obese subjects receiving exogenous administration of
ghrelin.
DESIGN: Randomised, double-blind, placebo-controlled study of intravenous ghrelin at doses 1 pmol/kg/min and 5 pmol/kg/
min.
SUBJECTS: In all, 12 healthy lean subjects (mean body mass index (BMI) 20.570.17 kg/m2) and 12 healthy overweight and
obese subjects (mean BMI 31.971.02 kg/m2).
MEASUREMENTS: Food intake, appetite and palatability of food, ghrelin and other obesity-related hormones, growth
hormone.
RESULTS: Low-dose infusion of ghrelin increased ad libitum energy intake at a buffet meal in the obese group only (mean
increase 36.679.4%, Po0.01.) High-dose ghrelin infusion increased energy intake in both groups (mean increase 20.1710.6%
in the lean and 70.1715.5% in the obese, Po0.01 in both cases.) Ghrelin infusion increased palatability of food in the obese
group.
CONCLUSION: Ghrelin increases food intake in obese as well as lean subjects. Obese people are sensitive to the appetite-
stimulating effects of ghrelin and inhibition of circulating ghrelin may be a useful therapeutic target in the treatment of obesity.
International Journal of Obesity (2005) 29, 1130–1136. doi:10.1038/sj.ijo.0803001; published online 24 May 2005

Keywords: appetite; ghrelin; food intake; growth hormone secretagogues

Introduction altered by the same volume of water.7 Chronic ghrelin

Ghrelin is a hormone synthesised in the stomach and is the 1 administration induces adiposity7 without attenuation of
endogenous ligand for the growth hormone secretagogue
receptor,2,3 which is expressed in hypothalamic nuclei
including the arcuate nucleus and in brain stem nuclei.4
Gastric expression and circulating levels of ghrelin are
upregulated by fasting.5–7
In rodents, ghrelin is a potent stimulus to feeding with
maximum effects observed within an hour of peripheral
administration.8 The resultant plasma levels are comparable
to those observed after a 24-h fast,6 suggesting physiological
relevance. Ghrelin levels fall after feeding. The mechanism
has not been identified, but the fall in level appears to be
influenced by gut nutrients rather than gastric distension as
plasma ghrelin is suppressed by an oral glucose load but not
*Correspondence: Professor SR Bloom, Department of Metabolic Medi-
cine, Imperial College, London, Hammersmith Hospital Campus, London,
UK.
E-mail: s.bloom@imperial.ac.uk
Received 11 October 2004; revised 21 February 2005; accepted 18 April
2005; published online 24 May 2005
the effects on food intake.6 In addition to its effects on
appetite, ghrelin stimulates gastric emptying and increases
gastric acid secretion in rodents.9
Human data also support a role for ghrelin in appetite
regulation.10 As in rodents, ghrelin is principally secreted by
the stomach and levels in postgastrectomy patients are
around 35% of those of age-matched controls.11 Plasma
levels rise preprandially and fall within 1 h of eating,12
suggesting that ghrelin may play a role in meal initiation as a
hunger signal.13 We have previously shown that exogenous
infusion of ghrelin at a dose of 5.0 pmol/kg/min increased
food intake at a buffet meal by 28% in normal weight human
subjects, compared to a saline control day.10 This was
associated with a preprandial increase in appetite, while
satiety after the meal was the same in both groups.
Fasting levels of several of the circulating hormones that
influence appetite regulation are different in obese people
compared with their lean counterparts. For example, leptin
is higher in obese people compared to lean14 and PYY levels
are lower in the obese.15 Some studies have observed

significantly lower basal levels of ghrelin in obese subjects
compared to lean16,17 and ghrelin changes with alterations
in body mass index (BMI), increasing after weight loss18,19
and falling with weight gain.20
Sensitivity to appetite-regulating hormones may also differ
between lean and obese groups. For example, while it was
hoped that leptin could be used to promote weight loss, it
proved ineffective in simple polygenic obesity, which is
associated with leptin resistance.14 In contrast, obese people
appear to retain sensitivity to the appetite-inhibiting
hormone PYY.15 There is evidence that the effect of ghrelin
on growth hormone secretion differs in lean and obese
individuals with a smaller response in the obese.21
It is not known whether obese individuals are responsive
to the appetite-stimulating effects of ghrelin. To establish
this would be a step towards greater understanding of the
role of ghrelin in the aetiology of obesity. In addition, this
may provide an insight into the potential utility of
modification of ghrelin as an approach to the treatment of
obesity.
Research design and methods
Subjects
Healthy lean and obese subjects were recruited by advertis-
ing in newspapers and on the Imperial College Campus in
London. Ethical approval was obtained from the local ethics
committee (project registration number 2000/5941) and the
study was performed in accordance with the principles of the
Declaration of Helsinki. In all, 24 subjects were recruited, 12
were lean and 12 were obese, with four males and eight
females in each group. The mean (7s.e.m.) BMI was
20.570.17 kg/m2 in the lean group and 31.971.02 kg/m2
in the obese group. All subjects were between the ages of 18
and 50 y (mean 24.771.34 for the lean group and 33.472.0
for the obese group) and all had had a stable body weight for
at least 3 months. The criteria for exclusion included
smoking more than five cigarettes a day, substance abuse,
pregnancy, use of medications except the oral contraceptive,
medical or psychiatric illnesses and abnormalities detected
on physical examination, electrocardiography or blood tests
(full blood count, electrolytes, liver function, random
glucose and thyroid function.) The subjects were screened
by a dietitian who assessed their eating behaviour with the
Dutch Eating Behaviour Questionnaire22 and the Eating
Attitudes Test Questionnaire.23 They also completed food
diaries to assess their usual dietary habits.
Protocol
The protocol design was based on previously published
studies.10,24,25 Each subject was studied on three occasions,
and received three infusions – saline, low-dose ghrelin
(1.0 pmol/kg/min) and high-dose ghrelin (5.0 pmol/kg/
min), in a double-blinded, randomised, crossover, Latin
Ghrelin in obese and lean subjects
MR Druce et al
1131
Square design. Each subject’s study days were at least 48 h
apart.
Food intake was standardised and recorded for the 24 h
prior to the study. All subjects fasted from 2100 h and drank
only water from midnight on the evening prior to each
study. Subjects refrained from alcohol and strenuous exercise
for 24 h before and after each study day.
Subjects arrived at 0830 h on each study day. Cannulae
were inserted into veins in both forearms, one for the
infusion of ghrelin or saline and the other for the collection
of blood samples. After venous cannulation, the subjects
relaxed for 30 min before the start of the study protocol.
Basal blood samples were taken at
30 and 0 min. All time
cues were removed from the study room and subjects were
encouraged to relax by reading and watching films. Infusions
commenced at 0900 h (t ¼ 0) and continued for a total of
75 min. Further blood samples were taken at 15, 30, 45 and
75 min of infusion, plus 30 min after the end of the infusion.
Blood samples were collected into plastic heparin-coated
tubes (LIP Ltd, UK) containing 5000 kallikrein inhibitor units
(0.2 ml aprotinin) (Bayer). Plasma was separated immediately
by centrifugation at 41C and stored at
201C until assayed.
At 45 min, while the infusions continued, a buffet meal
was served. All subjects had completed their meal by 75 min
at which time the infusion was terminated. Visual analogue
scales of 100 mm were used for rating hunger, nausea and
fullness at baseline and prebreakfast, and for assessment of
meal palatability after breakfast.26 The subjects left the study
room 30 min after cessation of the infusion and completed
food diaries until 1300 h the following day to allow
assessment of subsequent food intake. The food diaries were
analysed by a dietitian unaware of study assignments and
energy intake was calculated with the aid of Dietplan
(Forestfield Software Ltd, West Sussex, UK).
Dose
Subjects received infusion of either ghrelin 5.0 pmol/kg/min
in saline (high dose), or ghrelin 1.0 pmol/kg/min in saline
(low dose), or saline alone, in random order. These doses
were chosen on the basis of previous work carried out by the
Department of Metabolic Medicine at Imperial College,
London, in which an an intravenous infusion of ghrelin at
a dose of 5.0 pmol/kg/min led to a significant increase in
food intake in normal weight subjects at a test meal.10 The
lower dose of 1.0 pmol/kg/min was chosen in order to
highlight any difference in sensitivity to ghrelin between
the lean and obese groups. Infusion time was based on
previous ghrelin infusion protocols.
Meal
Subjects were instructed to eat as much as they wanted from
two standardised types of sandwiches, with fillings prear-
ranged with subjects to ensure a choice suitable for them,
and water to drink as required. Each subject received the
International Journal of Obesity
 Ghrelin in obese and lean subjects
MR Druce et al
1132
same meal on each study visit, and thus macronutrient
composition of the meal was constant. Food was offered in
sufficient excess to satisfy all appetites and subjects were
informed they could take away any uneaten food with them
if desired. The meal was completed at a single sitting, all
subjects having finished eating within 30 min while the
infusion continued. The amounts of food and water were
quantified preprandially and postprandially by a blinded
investigator and the caloric intake calculated.
Materials
Human ghrelin was obtained from Bachem (Merseyside,
UK.). The Limulus Amoebocyte Lysate Assay test for pyrogen
was negative and the peptide was sterile on culture. Peptide
was dissolved in 0.9% saline (Bayer, Haywards Heath, UK)
containing Haemaccel (Beacon, Kent, UK) (10% by volume)
to reduce adsorption to the syringe and tubing.
Assays
Ghrelin-like immunoreactivity was measured with an estab-
lished specific and sensitive radioimmunoassay.27–29 The
assay crossreacts fully (100%) with both octanoyl and des
octanoyl ghrelin and did not crossreact with any known
gastrointestinal or pancreatic peptide hormones. The anti-
sera (SC-10368) was obtained from Santa Cruz biotechnology
and used at a final dilution of 1:50 000. The 125I ghrelin was
prepared with Bolton & Hunter reagent (Amersham Inter-
national, UK) and purified by RP-HPLC using a linear
gradient from 10 to 40% acetonitrile, and 0.05% TFA over
90 min. The specific activity of ghrelin label was 48 Bq/fmol.
The assay was performed in total volume of 0.7 ml of 0.06 M
phosphate buffer pH 7.2 containing 0.3% BSA and was
incubated for 3 days at 41C before separation of free and
bound antibody by charcoal absorption. The assay detected
changes of 25 pmol/l of plasma ghrelin with 95% confidence
limit, with an intra-assay coefficient of variation 5.5%. All
samples were measured in one assay to avoid interassay
variation. Results were duplicated using a commercially
available kit (Phoenix Pharmaceuticals, Belmont, CA, USA.)
Insulin was measured using an established in-house radio-
immunoassay.30 Plasma leptin was measured with the Linco
Research kit (Missouri, USA). Growth hormone was quanti-
fied in the clinical reference laboratory by chemilumines-
cence immunoassay using the Nichols Advantage machine.
software.) Throughout, P-values less than 0.05 were con-
sidered significant.
Results
Subject characteristics
Subject characteristics are summarised in Table 1. The mean
BMI for the lean group was 20.5 kg/m2 with a range of 19.6–
21.5 kg/m2, selected to fall at the lean end of the range of
normal BMI. The mean BMI for the overweight and obese
subjects was 31.9 kg/m2, range 27.6–39 kg/m2. The mean
ages were 24.774.6 y in the lean group and 33.476.9 y in
the obese group. Leptin levels were lower in the lean group
(mean 6.2174.8 pmol/l) than in the obese group
(18.6877.8 pmol/l). Leptin levels differed markedly between
males and females. In the lean group, mean leptin was
1.8570.5 pmol/l for males and 8.3974.4 pmol/l for females.
In the obese group, mean leptin was 10.777.0 pmol/l for
males and 22.6674.9 pmol/l for females. Cholesterol was
higher in the obese group (5.5971.1 mmol/l) than in the
lean group (4.4670.9 mmol/l).
Plasma ghrelin
Mean basal ghrelin in the lean group was 459.6745.2 pmol/l
and in the obese group was 440.8749.1 pmol/l. There was no
statistically significant difference between the lean and obese
groups or between levels in males and females.
Ghrelin levels achieved are shown in Figure 1. Peak
premeal ghrelin levels achieved (at 45 min infusion) were
comparable in lean and obese groups for the low dose of
ghrelin. The peak in the lean group was 725.7741.3 pmol/l
and in the obese group 745.5740.4 pmol/l. These levels
correspond to 1.6- and 1.7-fold increases compared to the
ghrelin concentration in these groups at the same point on
the saline infusion day. The peak ghrelin level in the lean
group following high-dose ghrelin infusion was lower than
in the obese group with a value of 1598.27143.5 pmol/l as
compared to 2118.97139.9 pmol/l. With the high-dose
infusion, the peak ghrelin level reached was 3.6-fold greater
Table 1 Characteristics of lean and obese subjects taking part in the study
Lean Obese P-Value

Age (y) 24.774.6 33.476.9 0.002

BMI (kg/m2) 20.570.6 31.973.5 o0.001
Statistical analysis Fasting glucose (mmol/l) 4.2570.4 4.7370.3 o0.001
Subject characteristics are expressed as means 7s.d. Plasma Cholesterol (mmol/l) 4.4670.9 5.5971.1 0.01
Chol/HDL ratio 3.270.4 4.1270.6 o0.001
ghrelin hormone levels are expressed as means7s.e.m. The
Basal leptin (ng/ml) 6.2174.8 18.6877.8 0.0001
integrated area under the curve was calculated using the Fasting ghrelin (pmol/l) 459.67156.6 441.77171.0 0.78
trapezoid rule. Caloric intake is expressed as absolute kilo- Fasting insulin (pmol/l) 32.7711.7 46.2722.6 0.002
calories and as means7s.e.m., and as percentage change
Figures shown are mean and s.d. from the mean. Reference ranges for
compared to baseline saline day. Comparison within groups biochemical data: fasting glucose o6.2 mmol/l, fasting cholesterol 3.6–
having different treatments used paired t-tests (Sigmastat 6.5 mmol/l and chol/HDL ratio 3–5.

International Journal of Obesity


a saline low dose
ghrelin
3000
ghrelin pmol/l
2000
1000
0 **
-30 0 15 30 45 60
time (minutes)
b saline low dose
ghrelin
3000
ghrelin pmol/l
2000
1000
0
-30 0 15 30 45 60
time (minutes)
Figure 1 Mean ghrelin levels achieved over the course of infusions. Error
bars represent s.e.m. (a) Levels in the lean group and (b) Levels in the obese
group. High-dose ghrelin is 5.0 pmol/kg/min and low dose is 1.0 pmol/kg/
min. Infusion started at 0 min, meal served at 45 min and meal and infusion
ended at 75 min.
than at the same point during saline infusion in the lean
group, and five-fold greater in the obese group.
The areas under the curve over the 45 min infusion
showed no statistically significant difference for the low
dose, with values of 7.870.8 and 9.170.9 nmol/l/min for
the lean and obese groups, respectively. However, following
the high-dose infusion, the area under the curve was lower
for the lean than obese group with values of 31.872.2 and
42.872.6 nmol/l/min, respectively (P ¼ 0.02).
Effects of Ghrelin infusion on food intake
On the saline day, mean food intake for the obese group was
754.07136.9 kcal (3156.87573.2 kJ.) Mean food intake for
the lean group was 750.67106.5 kcal (3142.67445.9 kJ.) In
obese subjects, low-dose ghrelin infusion significantly
increased the energy intake on the ghrelin day compared
to the saline day: mean increase 165.8745.9 kcal
(694.27192.2 kJ), P ¼ 0.004. Low-dose exogenous ghrelin
infusion tended to increase energy intake in the lean group
compared to intake on the saline day; however, this was not
statistically significant: mean increase 128.7767.1 kcal
(538.87280.9 kJ), P ¼ 0.08. High-dose exogenous ghrelin
infusion increased energy intake in both the lean and obese
Ghrelin in obese and lean subjects
MR Druce et al
1133
high dose ghrelin ghrelin
ghrelin 1 pmol/kg/min 5 pmol/kg/min
200
**
food intake (% of baseline)
180
160
75 105
140
*
high dose
120
ghrelin
100
lean obese
Figure 2 Mean food intake in all groups as a percentage of intake on the
saline infusion day. Error bars show s.e.m. *P ¼ o0.05, **Po0.01. Baseline
mean intake on the saline control day was 750.67106.5 kcal in the lean group
and 754.07136.9 kcal in the obese group.
75 105
groups. In the obese group, the mean increase was
380.57100.0 kcal (1593.17418.7 kJ), where P ¼ 0.003 when
compared to saline. In the lean group, the mean increase was
118.1746.8 kcal (4944.67195.9 kJ), where P ¼ 0.004 when
compared to saline.
In percentage terms, the increases in energy intake during
the buffet meal following ghrelin infusion, as shown in
Figure 2, were as follows. In the obese group, the mean
increases were 36.679.4% on the low-dose day and 70.17
15.5% on the high-dose day. In the lean group, the mean
increases were 20.2710.8% on the low-dose infusion day
and 20.1710.6% on the high-dose day.
There was no effect on food intake in any group during the
24 h following the infusion, that is, there was no sustained
increase in food intake, nor was there a rebound reduction in
calories consumed following the cessation of infusion (data
not shown.)
Effects of ghrelin infusion on appetite and food
palatability
Infusion of ghrelin at low dose did not result in any
significant changes in scores of appetite or hunger, in either
lean or obese subjects, as measured by visual analogue scales.
Infusion of high-dose ghrelin resulted in an increase in score
for the question ‘how hungry do you feel’ in both lean and
obese subjects (P ¼ 0.004 and 0.03, respectively) and a fall in
score for the question ‘how full do you feel’ in both lean and
obese subjects (P ¼ 0.02 and 0.03, respectively) at 30 min
after injection. No subjects developed nausea during
infusion.
International Journal of Obesity
 Ghrelin in obese and lean subjects
1134
ghrelin
1 pmol/kg/min
140
palatability (% of saline day)
130
120
110
100
90
80
lean
Figure 3 Subjects ratings of palatability of test meal as a percentage of
palatability on the saline control day. Error bars represent s.e.m. *Po 0.05.
Visual analogue scores for the palatability of the food
offered at the buffet breakfast (Figure 3) showed no
significant differences between infusion days in the lean
group. In the obese group, palatability was increased by a
mean of 17.577.4% compared to saline on the low-dose
infusion day and 21.378.7% compared to saline on the
high-dose infusion day (P ¼ 0.04 in both cases) (Figure 3).
Effects of ghrelin infusion on growth hormone
secretion
Peak growth hormone was achieved at 45 min after the start
of the infusion of ghrelin. After low dose, the mean growth
hormone increment from baseline to peak (compared to that
on the saline day) was 40.378.8 mIU/l in the lean group and
20.874.7 mIU/l in the obese group (P ¼ 0.06). At high dose,
the increment in the lean group was 201.2743.7 mIU/l in
the lean group and 69.3717.8 mIU/l in the obese group
(P ¼ 0.01.) This is shown in Figure 4.
Discussion
Ghrelin is a circulating hormone shown to promote feeding
and adiposity following administration in rodents.6,7 In
addition, ghrelin stimulates appetite and food intake in
humans.10 In this current investigation, we aimed to
investigate whether ghrelin acts to increase appetite and
food intake in obese individuals. This finding may provide
insight into the aetiology of obesity and would also help to
elucidate whether ghrelin would be a suitable candidate as a
therapeutic target in the treatment of obesity. Other groups
have observed a difference in fasting plasma ghrelin
concentrations between lean and obese humans, with higher
ghrelin levels in lean individuals.16,17 These observations
have led to the hypothesis that ghrelin acts as a counter-
regulatory hormone, rising in lean people to stimulate
appetite and weight gain and falling in obesity to limit
energy intake. The different basal levels may be reflected in
International Journal of Obesity
MR Druce et al
ghrelin 250
5 pmol/kg/min lean
peak GH increment (mIU/l)
obese
* 200
*
150
**
100
50
obese 0
1 pmol/kg/min 5 pmol/kg/min
Ghrelin dose
Figure 4 Effect of ghrelin infusion on growth hormone secretion. Peak
growth hormone increment at 45 min (compared to change in growth
hormone on saline day) is expressed in mIU/l. Error bars represent s.e.m. For
the low dose *P ¼ 0.06 and for the high dose **P ¼ 0.01.
different responsiveness to the appetite-stimulating effects of
ghrelin. Furthermore, there is some evidence to suggest that
the normal postprandial fall in ghrelin is attenuated in the
obese.31 This could result in decreased postprandial satiety,
further increasing food intake. The mechanism underlying
the decreased ghrelin associated with obesity remains
unclear.
In this study, we found no significant difference in basal
ghrelin levels between the lean and obese individuals. This
finding was somewhat surprising. The ghrelin measurements
were repeated with a widely available commercial assay
(Phoenix Pharmaceuticals, Belmont, CA, USA), which con-
firmed the initial findings with our assay. However, the lean
and obese groups clearly differed with respect to BMI, leptin,
insulin and cholesterol levels as expected. The observation
that circulating ghrelin is inversely proportional to BMI
comes from investigations of subjects including more
individuals at the extremes of the BMI range.16 Other studies
have focused on such extremes, for example, many subjects
with BMI o18.5 due to anorexia nervosa in one17 and
severely obese subjects with BMI 33–65 kg/m2 in another.32
The relationship between BMI and ghrelin is nonlinear.33 A
significant difference may be more difficult to demonstrate
in our cohort of volunteers, who were purposely chosen with
a narrower BMI range (19.6–39 kg/m2) in order to more
closely reflect the spectrum of body weight in healthy
normal weight and overweight individuals. Indeed, other
published studies have also used cohorts of healthy lean and
obese subjects with no difference in basal ghrelin.34
Although mean fasting ghrelin levels do not differ between
the two groups, other classical markers of obesity are altered
as expected in our cohort. Thus basal leptin and insulin
levels and fasting cholesterol are all higher in the obese
group.
Low-dose ghrelin infusion led to similar plasma levels in
the lean and obese groups. Overall the circulating ghrelin

level reached at the time of presentation of the buffet meal
was similar (1.6 and 1.7 times the level seen at the same
point on the saline infusion day) with a comparable
cumulative elevation of plasma ghrelin in each case (as
estimated by area under the curve.) In comparison the high
dose resulted in a significant difference in plasma concen-
tration at the time of presentation of the meal and also in
total area under the curve between the lean and obese
groups. Therefore, we have applied statistical calculations to
both doses administered (reflecting the experimental de-
sign), but for the purposes of this discussion, we will focus
mainly on the food intake results obtained following low-
dose infusion. This will enable comparison of the effects of
equivalent plasma levels of ghrelin achieved in the two
groups.
The low-dose infusion of ghrelin, which led to a peak
ghrelin level of 1.6–1.7 times that observed on the saline
control day, resulted in a mean increase of 20.2% in food
intake in the lean group and 36.6% in the obese group. This
change was statistically significant for the obese group
(Po0.05), and thus it is clear that obese people retain
sensitivity to exogenous infusion of ghrelin. It may be noted
that after high-dose infusion, there was a mean increase in
food intake of 20.1% in the lean group and 70.1% in the
obese group. In both groups, the high dose led to a
statistically significant increase in food intake compared to
the saline control day (Po0.05 and o0.01, respectively).
However, the differences in plasma levels achieved after high
dose in the lean and obese groups preclude further analysis.
It is helpful to examine the food intake response following
intravenous ghrelin in published work, although direct
comparison would not be valid due to differences in infusion
duration and experimental paradigm. Wren et al10 reported
that an intravenous infusion of ghrelin of 5 pmol/kg/min
resulted in a 28% increase in food intake.
Visual analogue scores of hunger and fullness did not show
statistically significant differences compared to saline in the
lean group following administration of ghrelin. However, in
the obese group, low-dose ghrelin increased the palatability
of food at the buffet meal by a mean of 17.5% and high dose
by 21.3% (Po0.05 in both cases). It could be that enhance-
ment of food palatability following ghrelin administration
resulted in the increased food intake.
These findings indicate that ghrelin sensitivity is retained
in obese individuals and therefore ghrelin receptor antago-
nists may prove to be useful appetite-reducing agents.
Further studies of the effects of ghrelin antagonists in both
normal weight and obese humans are now warranted to test
this further. There is some evidence of reduced food intake in
rodents following administration of ghrelin antagonists,35
but the effects of these agents in human subjects have not
been investigated.
A further interesting observation in our study is the effect
of ghrelin administration on the growth hormone response.
Obesity is characterised by several endocrine abnormalities
including reduction of both spontaneous and stimulated
Ghrelin in obese and lean subjects
MR Druce et al
1135
growth hormone secretion. It has been postulated that the
effect could be due to the lower endogenous levels of growth
hormone secretagogues such as ghrelin. However, in our
study, the growth hormone response in the obese group is
blunted at both doses of ghrelin administered despite
endogenous fasting ghrelin concentrations, which did not
differ significantly from those of the lean group. This
contrasts with the maintained effect of ghrelin on food
intake in the obese group. At the high dose in particular, the
obese group had a significantly higher mean ghrelin level
(1.3 times that of the lean group) yet the growth hormone
response was almost three times as great in the lean group.
This corroborates the impairment in growth hormone
response to ghrelin in the obese observed by other groups.21
Interestingly, the growth hormone response to ghrelin is also
blunted in patients with anorexia nervosa who have high
ghrelin levels.36 In our cohort, the effect may also be
enhanced by the greater age in the obese group, as age also
results in a blunting of the growth hormone response to
ghrelin.37
In summary, we have observed that the feeding response
to ghrelin is maintained in obesity. In contrast, the growth
hormone response to ghrelin is attenuated. Ghrelin is a
stimulus to food intake and its effects may contribute to the
aetiology of obesity. Furthermore this highlights ghrelin as a
potential therapeutic target in strategies to treat obesity.
Further work with ghrelin-blocking agents is indicated to
elucidate this further.
Acknowledgements
We Dr M Donaldson and Mr JH Meek for growth hormone
assays, Professor M Allison for peptide testing, and the Sir
John McMichael Centre for providing the facility for studies
with human volunteers. MD, AW and AP are funded by
Wellcome Trust Clinical Research Training Fellowships, MP is
funded by a grant from the BBSRC. This work is supported by
a programme grant from the Wellcome Trust.
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