Ghrelin, the set point hormone?

[Guest guest]

Of course we are all suspicious about the so called set point

theory... I don't know if this resolves anything but what I really

want to know it who how and why, " grrelin? "

Hormone Wants To Keep Body At Weight Set Point

http://www.sciencedaily.com/releases/2004/07/040707091615.htm/

Studies of a stomach hormone called ghrelin in normal weight women

indicate that the hormone may play a part in reestablishing a body

weight set-point after dieting and exercise, according to Penn State

researchers.

" Most studies have analyzed physical levels of ghrelin in obese

or

anorexic subjects, " says J. Leidy, who recently received her

Ph.D. in physiology. " We looked at ghrelin in healthy, normal weight

women. We are trying to see how the body maintains weight and

maintains its energy balance. "

Prior research showed that ghrelin levels rise when fasting and fall

when the subject is fed. The levels rise 60 to 30 minutes before a

normal meal time and 30 to 60 minutes after a meal, the level drops.

According to Leidy, studies in human and rodents have found that

injections of ghrelin significantly increase both hunger and food

intake.

The researchers, led by I. , associate professor of

kinesiology, wanted to determine if ghrelin release was associated

with body weight, physical exercise, reduced food intake or an

overall energy deficit.

" Changes in ghrelin appear to be most sensitive to changes in body

weight created by an overall energy deficit, independent of specific

effects of reduced food intake or physical exercise, " the researchers

reported in a recent issue of the journal, Clinical Endocrinology &

Metabolism.

The researchers, who also included J.K. Gardner, research associate;

B.R. Frye, graduate student; and M.L. Snook, M.K. Schuchert, and E.L.

, undergraduate students, looked at healthy women without

eating disorders, between the ages of 18 and 30, weighing between 105

and 160 pounds with 15 to 30 percent body fat. The women were non-

smokers, not taking hormonal contraceptives and had no significant

weight loss or gain in the past year. The study was part of a larger

one designed to assess changes in reproductive function in response

to controlled feeding and exercise.

Participants had to agree to eat only food provided by the Penn State

General Clinical Research Center at University Park and to eat two of

their three meals at the facility. In the initial study, researchers

studied all participants for about a month to establish a baseline;

the subjects followed the controlled diet and exercise plans for

three months. Researchers randomly assigned women to four groups, a

control group that did no exercise and were given enough calories to

maintain their weight, a group that exercised but were given enough

calories to maintain their weight, and two groups that exercised but

were given fewer calories than required to maintain their weight. One

energy deficit group had a moderate energy deficit and the other had

a high-energy deficit.

For the ghrelin study, the four groups were compressed to three: the

control group, the weight stable exerciser group and the weight loss

exerciser group. Because the participants' diets were closely

controlled, those that exhibited a weight loss, clearly experienced

an energy deficit caused by exercise.

The researchers measured body fat, fat mass and fat-free mass before

the study, at the study midpoint and after the study. They also

measured resting metabolic rate and maximal aerobic capacity. Blood

samples to measure ghrelin level were done on 22 subjects and

midpoint measurements on 17 subjects.

" The disruption of body weight regulation seen in obesity makes one

examine physiological factors in short and long term energy balance, "

says Leidy. " This is the first study to show that weight loss

resulting from a diet and exercise intervention leads to an increase

in circulating ghrelin in normal weight, healthy young women. We

found that ghrelin was significantly elevated with weight loss in

exercising subjects. "

The researchers found that changes in ghrelin came after changes in

body weight, composition and resting metabolic rate. Previous

research showed that ghrelin levels are low in obese subjects and

high in anorexic subjects, however, in the study's normal women, no

correlation between baseline ghrelin and body weight, body mass

index, percent body fat, fat mass or fat-free mass was found. The

researchers state that ghrelin levels reflect energy status and body

composition only in subjects who have experienced significant

alterations in energy status rather than the relatively stable energy

and body composition status of the study's subjects.

" The stimulatory effect on food intake attributed to ghrelin suggests

a potential role for ghrelin in returning the body to a prior set-

point for body weight after weight loss, " the Penn State researchers

report. " The absence of changes in ghrelin in our weight stable group

demonstrates that exercise training itself has little impact on at

least one powerful modulator of food intake. "

" The increase in ghrelin in the weight loss group was in response to

the overall energy deficit created by the combination of reduced food

intake and exercise, and not due to the endocrine and/or metabolic

effects of physical exercise itself, " says Leidy.

The National Institutes of Health supported this research.

[Guest guest]

Hi All,

CR may involve use of the ghrelin receptor for determining the set

point for regulating our appetite?

See the pdf-available below.

Holst B, Schwartz TW.

Constitutive ghrelin receptor activity as a signaling set-point in

appetite

regulation.

Trends Pharmacol Sci. 2004 Mar;25(3):113-7. Review. No abstract

available.

PMID: 15058279 [PubMed - indexed for MEDLINE]

Ghrelin plays a key role as the major orexigenic hor-mone

from the gastrointestinal tract to the hypothala-mic

areas that govern food intake, balancing against a

multitude of anorectic hormones, such as leptin, insulin

and PYY3–36 . Surprisingly, even in the absence of ago-nist,

the ghrelin receptor signals with ~50% activity.

Thus, although ghrelin receptor antagonists are

expected to reduce meal-associated food intake, inverse

agonists of the ghrelin receptor, by blocking the consti-tutive

receptor activity, might lower the set-point for

hunger between meals, eliminating the craving for

second orders, desserts and snacks.

Long before the discovery of ghrelin, peptide and non-peptide

compounds were synthesized and optimized as so-called

growth hormone secretagogs [1]. In the mid-1990s

the G-protein-coupled seven-transmembrane receptor

through which these compounds acted was cloned [2],

but the endogenous ligand for this receptor – ghrelin –

was not identified until 1999 [3]. This 28 amino acid

peptide is unusual because its biological activity depends

on an n-octanylation at position Ser3 [3]. Surprisingly, the

main site of production of ghrelin was found to be

endocrine cells in the upper gastrointestinal (GI) tract,

and the major physiological role of ghrelin appears to be in

the control of food intake and energy homeostasis [4].In

humans, ghrelin infusion increases appetite and food

intake both in normal subjects and in patients with

decreased appetite, such as those suffering from cancer

cachexia [5].

Ghrelin: the major orexigenic hormone that constitutes a

pre-meal signal for food intake

Rather abruptly, 20–30 min before a meal ghrelin is

released from endocrine cells found mainly in the fundic

mucosa of the stomach, although only when the upper GI

tract is empty of calories [6,7]. The surge in plasma ghrelin

levels drops shortly after food reaches the stomach [6,8].

Thus, `it is possible that in the conditioned animal, or

human subject, the CNS in the expectation of an upcoming

meal sends signals to " ask " whether the local conditions in

the GI tract are appropriate for food intake' (Steve Woods).

If food is not present in the upper GI tract, ghrelin is

secreted to `tell' the hypothalamic centers that it is `OK' to

start eating (i.e. ghrelin provides a sensation of hunger).

Ghrelin stimulation balances against a multitude of

inhibitory signals on the NPY/AGRP-containing neurons

A major target for ghrelin is the arcuate nucleus of the

hypothalamus. This nucleus harbors two populations of

neurons with parallel projections but opposing effects on

food intake and energy balance [9]. Both groups of neurons

project heavily to the paraventricular nucleus of the

hypothalamus, where their neurotransmitters are

believed to exert their anorectic (appetite-suppressing)

or orexigenic (appetite-stimulating) action [10]. The

appetite-stimulating groups of neurons, which express

the potent orexigenic neuropeptides neuropeptide Y (NPY)

(stimulating NPY Y1 and Y5 receptors) and agouti-related

protein (AGRP) (blocking melanocortin MC3 and MC4

receptors), appear to be the major target for ghrelin. These

NPY/AGRP-containing neurons express ghrelin receptors

[11] and respond to ghrelin by increasing their firing rate

[12]. The anorectic pools of arcuate neurons express

transmitters derived from proopiomelanocortin

(POMC) and cocaine and amphetamine-regulated tran-script

(CART) but do not possess ghrelin receptors [12].

Nevertheless, local projections from NPY/AGRP-containing

neurons terminate on the POMC/CART-containing

neurons and release GABA when activated

by ghrelin; thus, these anorectic neurons are indirectly

inhibited by ghrelin [12].

Both the NPY/AGRP- and the POMC/CART-containing

neurons are targets for several inhibitory signals for food

intake. Importantly, on a long-term basis, the hormones

leptin and insulin act through their respective receptors on

NPY/AGRP-containing neurons (and on POMC-contain-ing

neurons) to inhibit food intake [10,13]. Additionally,

the L-cell-derived hormone PYY3–36 [co-released with

glucagon-like peptide 1 (GLP-1) from the lower GI tract

following food intake] has been proposed to inhibit food

intake by acting on presynaptic Y2 receptors [14]. Thus, on

the NPY/AGRP-containing neurons the ghrelin receptor

provides the only hormonal, appetite-stimulatory input

that counterbalances a large number of inhibitory

inputs [10] (Figure 1).

Recently, using surgical and chemical vagotomy, a

solid case was presented for the notion that afferent

vagal neurons might be an alternative and important

target for the stimulatory effect of ghrelin on food

intake [15]. The appetite regulatory signals from the

gut are conveyed to the hypothalamus through the

afferent vagus and the nucleus of the solitary tract

(NTS)in thebrain stem[15].In fact,ghrelin receptors

are also found in the dorsal vagal complex, making this

another target for circulating ghrelin [15].Thus,

although the major focus has been on the hypothalamic

ghrelin receptor, several other sites that are important

in appetite regulation could be involved in mediating

ghrelin-induced food intake (Figure 1). Interestingly, it

appears that the ghrelin receptor is coexpressed with

the leptin receptor in these locations [15,16].

Does the high constitutive activity of the ghrelin receptor

provide a set-point for appetite regulation between

meals?

Figure 1. The possible dual hormonal and neuronal route for

ghrelin as an orexigenic (appetite-stimulating) signal from the

gastrointestinal (GI) tract to the hypothalamus.

Ghrelin stimulates food intake, balancing against several inhibitory

signals (e.g. insulin, leptin and PYY3–36) from the periphery to the

arcuate nucleus of the hypothalamus.

Ghrelin as a hormone can, in principle, increase food intake by

either stimulating neuropeptide (NPY) and agouti-related protein

(AGRP)-containing neurons in the arcuate

nucleus or acting indirectly through the dorsal vagal complex in the

nucleus tractus solitarius (NTS) in the brain stem. Note the

inhibitory pathway from NPY/AGRP-contain-ing

neurons to proopiomelanocortin (POMC) and cocaine and amphetamine-

regulated transcript (CART)-containing neurons, through which ghrelin

receptor activity can

indirectly inhibit the latter neurons. Ghrelin also acts by

stimulating mainly gastric afferent vagal fibers [15], conceivably in

a paracrine manner when released from the

endocrine cells in the gut. Abbreviations: CCK, cholecystokinin; CRF,

corticotropin-releasing factor; MCH, melanin-concentrating hormone;

PVN, paraventricular nucleus.

Does the high constitutive activity of the ghrelin receptor

provide a set-point for appetite regulation between

meals?

Recently, it was shown that the ghrelin receptor exhibits

high constitutive activity. This receptor property remained

inositol (1,4,5)-trisphosphate [ins(1,4,5)P3] turnover was

measured instead it became clear that the ghrelin receptor

in the absence of agonist signals with ,50% efficacy

(Figure 2). As expected, ghrelin and various non-peptide

growth hormone secretagogs also act as agonists in

respect of increasing Ins(1,4,5)P3 turnover. Importantly,

a highly modified substance P analog, [D-Arg1,D-Phe5,

D-Trp7,9,Leu11]-substance P, known to be a low-potency

blocker of agonist-stimulated signaling, was found

to be a highly potent, full inverse agonist, decreasing the

constitutive signaling of the ghrelin receptor down to that

observed in mock transfected cells [17].

Although the primary transducer molecule is Gqa, the

high constitutive activity of the ghrelin receptor results in

a robust ligand-independent activation of cAMP respon-sive

element (CRE)-mediated gene transcription concei-vably

conveyed through Ca 2 þ –calmodulin-dependent

kinase IV-mediated phosphorylation of CRE-binding pro-tein

(CREB) [18] (Figure 2). Importantly, control of CREB

activity was recently shown in vivo to be a major signal

transduction pathway for leptin in NPY/AGRP-containing

neurons of the hypothalamus [19]. Thus, this represents

part of a common signaling pathway for the physiologically

opposing actions of ghrelin and leptin (Figure 2).

As described above, ghrelin appears to counterbalance

several inhibitory inputs at its various sites of action

(Figures 1,3). Although the constitutive activity of the

ghrelin receptor remains to be shown in an in vivo setting,

the high constitutive signaling of the ghrelin receptor

could provide a set-point of signal transduction activity

against which all the inhibitory receptors act. For

example, a decrease in leptin levels is an important signal

for increased food intake and decreased energy expendi-ture.

This leptin signal could be mediated through a

decreased downstream inhibition of the constitutive

signaling of the ghrelin receptor, causing an increase in

food intake (Figures 2,3).

Obesity: ghrelin receptor antagonists before meals and

inverse agonists between meals?

It has become increasingly clear that ghrelin receptor

antagonists could be highly interesting anti-obesity drugs

as blockers of the orexigenic signal from the GI tract to the

brain [7]. Importantly, however, the hormonal ghrelin

signal occurs only just before and at the start of a meal.

Nevertheless, it is well known that many people feel

enough `hunger' to nibble between meals, despite the fact

that ghrelin levels have returned to pre-meal levels at this

point (Figure 3). If the constitutive activity of the ghrelin

receptor, as suggested, provides a signaling set-point in the

stimulatory branch for food intake between meals, then

inverse agonists for the ghrelin receptor might reduce

`between-meals' food intake. The rationale behind this is

that blocking the constitutive activity of the ghrelin

receptor should increase sensitivity to inhibitory signals

such as leptin, insulin and PYY3–36, and thereby eliminate

unnoticed for many years because mobilization of intra-cellular

Ca 2 þ had been used almost exclusively to monitor

the signal transduction activity of the receptor [17]. When

the craving for second meals, desserts and snacks

(Figure 3). Interestingly, as illustrated by the substance

P analog, it is possible to develop selective inverse agonists

with high potency as inverse agonists but with a much

lower potency as antagonists (Figure 2). It could be

hypothesized that a selective inverse agonist would be

the correct remedy to sustain a weight loss because at the

correct dose the drug would decrease the constitutive

activity of the ghrelin receptor between meals but would

still allow for appropriate food intake during meals. This

hypothesis can only be tested by an in vivo trial of a

selective inverse agonist for the ghrelin receptor, prefer-entially

a non-peptide compound having a better `thera-peutic

window' than the substance P analog, which at

higher doses has unspecific effects on other receptors.

Unfortunately, however, all publicly available non-peptide

compounds are either agonists or neutral antagonists [17].

Figure 2. High constitutive signaling by the ghrelin receptor

through the Gqa pathway, including activation of cAMP response

element (CRE)-mediated gene transcription.

(a) Inositol (1,4,5)-trisphosphate [ins(1,4,5)P3] turnover in

response to the application of the endogenous agonist ghrelin, the

non-peptide growth hormone (GH) secretagog

MK677 (see Chemical names) and the full inverse agonist [D-Arg1,D-

Phe5,D-Trp7,9,Leu11]-substance P (SP) is shown in COS cells

transfected with the ghrelin receptor. Note

that the SP analog displays higher potency as an inverse agonist

compared with as an antagonist.

( CRE-luciferase activity is shown in a gene-dosing experiment with

the

ghrelin receptor in HEK-293 cells. © A highly simplified signal

transduction scheme demonstrating the convergence of the stimulatory

ghrelin signal and the inhibitory

leptin signal on CRE-binding protein (CREB) is shown (curves are

redrawn from [17]).

–

Regulation of ghrelin receptor _expression provides a

direct control of signaling activity

The fact that the ghrelin receptor signals with very high

activity independently of the agonist implies that control

of the _expression level of the receptor is directly correlated

to signaling activity (Figure 2b). During prolonged fasting

an eightfold increase in the _expression of the ghrelin

receptor in the hypothalamus was described recently [20].

This would be expected to result in a ghrelin-independent

increase in receptor signaling and thereby an appropriate

general increase in appetite and decrease in energy

expenditure. Moreover, polymorphisms that result in

altered _expression of the receptor protein should directly

result in an altered signaling and thereby altered

regulation of appetite, independently of the ghrelin ligand.

For example, single nucleotide polymorphisms that lead to

increased ghrelin receptor _expression should be expected

to be associated with obesity.

Figure 3. Inverse agonists for the ghrelin receptor as anti-

obesity drugs? Plasma levels of ghrelin increase 20–30 min before

meal (pre-meal surge) [6]. Thus, in obesity,

ghrelin receptor antagonists could be used to block this

ghrelin `stimulus' and thereby reduce meal size [17]. By contrast,

inverse agonists for the ghrelin receptor that

specifically target its constitutive activity might be efficient

drugs to lower the signaling set-point between meals and thereby

increase sensitivity to the multiple inhibitory

signals (e.g. leptin, insulin and PYY3–36) and consequently eliminate

snack-eating behavior. Abbreviations: AGRP, agouti-related protein;

B, breakfast; L, lunch; MC4, mela-nocortin

receptor type 4; NPY, neuropeptide Y; Y1, NPY receptor type 1.

Chemical names

MK677: N-[1®{[1,2-dihydro-1-methanesulfonylspiro-(3H-

indole-3,4'-yl]carbonyl}-2-(phenylmethoxy)-

ethyl]-2-amino-2-methylpropanamide methanesulfonate

References

1 Bowers, C.Y. et al. (1980) Structure-activity relationships of a

synthetic pentapeptide that specifically releases growth hormone in

vitro. Endocrinology 106, 663–667

2 , A.D. et al. (1996) A receptor in pituitary and hypothalamus

that functions in growth hormone release. Science 273, 974–977

3 Kojima, M. et al. (1999) Ghrelin is a growth-hormone-releasing

acylated peptide from stomach. Nature 402, 656–660

4 Kojima, M. et al. (2001) Ghrelin: discovery of the natural

endogenous

ligand for the growth hormone secretagogue receptor. Trends

Endocrinol. Metab. 12, 118–122

5 Wren, A.M. et al. (2001) Ghrelin enhances appetite and increases

food

intake in humans. J. Clin. Endocrinol. Metab. 86, 5992

6 Cummings, D.E. et al. (2001) A preprandial rise in plasma ghrelin

levels suggests a role in meal initiation in humans. Diabetes 50,

1714–1719

7 Cummings, D.E. et al. (2002) Plasma ghrelin levels after diet-

induced

weight loss or gastric bypass surgery. New Engl. J. Med. 346,

1623–1630

8 Drazen, D.L. et al. (2003) Peripheral signals in the control of

satiety

and hunger. Curr. Opin. Clin. Nutr. Metab. Care 6, 621–629

9 Tschop, M. et al. (2000) Ghrelin induces adiposity in rodents.

Nature

407, 908–913

10 Schwartz, M.W. et al. (2000) Central nervous system control of food

intake. Nature 404, 661–671

11 Willesen, M.G. et al. (1999) Co-localization of growth hormone

secretagogue receptor and NPY mRNA in the arcuate nucleus of the

rat. Neuroendocrinology 70, 306–316

12 Cowley, M.A. et al. (2003) The distribution and mechanism of

action of

ghrelin in the CNS demonstrates a novel hypothalamic circuit

regulating energy homeostasis. Neuron 37, 649–661

13 Crowley, V.E. et al. (2002) Obesity therapy: altering the energy

intake-and-expenditure balance sheet. Nat. Rev. Drug Discov. 1,

276–286

14 Batterham, R.L. et al. (2002) Gut hormone PYY(3–36) physiologically

inhibits food intake. Nature 418, 650–654

15 Date, Y. et al. (2002) The role of the gastric afferent vagal

nerve in

ghrelin-induced feeding and growth hormone secretion in rats.

Gastroenterology 123, 1120–1128

16 Cummings, D.E. et al. (2003) Ghrelin–leptin tango in body-weight

regulation. Gastroenterology 124, 1532–1535

17 Holst, B. et al. (2003) High constitutive signaling of the ghrelin

receptor-identification of a potent inverse agonist. Mol. Endocrinol.

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2201–2210

18 s, R.P. et al. (1994) Calcium/calmodulin-dependent protein

kinase types II and IV differentially regulate CREB-dependent gene

_expression. Mol. Cell. Biol. 14, 6107–6116

19 Shimizu-Albergine, M. et al. (2001) Downregulation of fasting-

induced

cAMP response element-mediated gene induction by leptin in

neuropeptide Y neurons of the arcuate nucleus. J. Neurosci. 21,

1238–1246

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1317–1320

Cheers, Alan Pater

> Of course we are all suspicious about the so called set point

> theory... I don't know if this resolves anything but what I really

> want to know it who how and why, " grrelin? "

>

> Hormone Wants To Keep Body At Weight Set Point

>

> http://www.sciencedaily.com/releases/2004/07/040707091615.htm/

>

> Studies of a stomach hormone called ghrelin in normal weight women

> indicate that the hormone may play a part in reestablishing a body

> weight set-point after dieting and exercise, according to Penn

State

> researchers.

> " Most studies have analyzed physical levels of ghrelin in obese

> or

> anorexic subjects, " says J. Leidy, who recently received

her

> Ph.D. in physiology. " We looked at ghrelin in healthy, normal

weight

> women. We are trying to see how the body maintains weight and

> maintains its energy balance. "

> Prior research showed that ghrelin levels rise when fasting and

fall

> when the subject is fed. The levels rise 60 to 30 minutes before a

> normal meal time and 30 to 60 minutes after a meal, the level

drops.

> According to Leidy, studies in human and rodents have found that

> injections of ghrelin significantly increase both hunger and food

> intake.

> The researchers, led by I. , associate professor of

> kinesiology, wanted to determine if ghrelin release was associated

> with body weight, physical exercise, reduced food intake or an

> overall energy deficit.

> " Changes in ghrelin appear to be most sensitive to changes in body

> weight created by an overall energy deficit, independent of

specific

> effects of reduced food intake or physical exercise, " the

researchers

> reported in a recent issue of the journal, Clinical Endocrinology &

> Metabolism.

> The researchers, who also included J.K. Gardner, research

associate;

> B.R. Frye, graduate student; and M.L. Snook, M.K. Schuchert, and

E.L.

> , undergraduate students, looked at healthy women without

> eating disorders, between the ages of 18 and 30, weighing between

105

> and 160 pounds with 15 to 30 percent body fat. The women were non-

> smokers, not taking hormonal contraceptives and had no significant

> weight loss or gain in the past year. The study was part of a

larger

> one designed to assess changes in reproductive function in response

> to controlled feeding and exercise.

> Participants had to agree to eat only food provided by the Penn

State

> General Clinical Research Center at University Park and to eat two

of

> their three meals at the facility. In the initial study,

researchers

> studied all participants for about a month to establish a baseline;

> the subjects followed the controlled diet and exercise plans for

> three months. Researchers randomly assigned women to four groups, a

> control group that did no exercise and were given enough calories

to

> maintain their weight, a group that exercised but were given enough

> calories to maintain their weight, and two groups that exercised

but

> were given fewer calories than required to maintain their weight.

One

> energy deficit group had a moderate energy deficit and the other

had

> a high-energy deficit.

> For the ghrelin study, the four groups were compressed to three:

the

> control group, the weight stable exerciser group and the weight

loss

> exerciser group. Because the participants' diets were closely

> controlled, those that exhibited a weight loss, clearly experienced

> an energy deficit caused by exercise.

> The researchers measured body fat, fat mass and fat-free mass

before

> the study, at the study midpoint and after the study. They also

> measured resting metabolic rate and maximal aerobic capacity. Blood

> samples to measure ghrelin level were done on 22 subjects and

> midpoint measurements on 17 subjects.

> " The disruption of body weight regulation seen in obesity makes one

> examine physiological factors in short and long term energy

balance, "

> says Leidy. " This is the first study to show that weight loss

> resulting from a diet and exercise intervention leads to an

increase

> in circulating ghrelin in normal weight, healthy young women. We

> found that ghrelin was significantly elevated with weight loss in

> exercising subjects. "

> The researchers found that changes in ghrelin came after changes in

> body weight, composition and resting metabolic rate. Previous

> research showed that ghrelin levels are low in obese subjects and

> high in anorexic subjects, however, in the study's normal women, no

> correlation between baseline ghrelin and body weight, body mass

> index, percent body fat, fat mass or fat-free mass was found. The

> researchers state that ghrelin levels reflect energy status and

body

> composition only in subjects who have experienced significant

> alterations in energy status rather than the relatively stable

energy

> and body composition status of the study's subjects.

> " The stimulatory effect on food intake attributed to ghrelin

suggests

> a potential role for ghrelin in returning the body to a prior set-

> point for body weight after weight loss, " the Penn State

researchers

> report. " The absence of changes in ghrelin in our weight stable

group

> demonstrates that exercise training itself has little impact on at

> least one powerful modulator of food intake. "

> " The increase in ghrelin in the weight loss group was in response

to

> the overall energy deficit created by the combination of reduced

food

> intake and exercise, and not due to the endocrine and/or metabolic

> effects of physical exercise itself, " says Leidy.

> The National Institutes of Health supported this research.