Sleep - = weight +

December 8, 2004

Hi All,

According to:

http://www.cnn.com/2004/HEALTH/diet.fitness/12/06/sleep.weight.gain.re

ut/index.html

sleep loss results in weight gain.

CRers appear to require less sleep on average than ad

libbers. We are also highly concerned regarding control

of our appetites to maintain our CR status. So, the report

now published should be in our interest. Try to maintain

an even keel on sleep level at the predictable time each

day and phase of the outdoor light cycle to match our

internal circadian rhythm. This might be our take-home

message from the below.

However, the article has been published albeit not yet

reported by Medline. It and related papers are presented

largely verbatim below.

A Good Night's Sleep: Future Antidote to the Obesity Epidemic?

S. Flier and K. Elmquist

Ann Intern Med 2004;141 885-886

In this issue, Spiegel and colleagues raise much food for

thought (so to speak). If their findings on changes in leptin and

ghrelin during sleep deprivation are reproducible and generalizable,

and if these hormonal changes cause changes in food intake over time,

we may add inadequate sleep to the environmental factors that

contribute to weight gain and obesity.

It is well established that the prevalence of obesity has

been increasing over recent decades, both in the United

States and the rest of the developed world. Why is this

happening? Body weight is physiologically regulated, and

this regulation involves a complex physiologic system en-coded

by an array of specific genes (1). This system in-volves

both central and peripheral components and inter-acts

with aspects of the environment, such as availability

and composition of the diet and the need for physical ex-ercise,

to influence body weight. Although genes play a

critical role in weight determination, the increased preva-lence

in obesity of populations over a period of decades is

induced by changes in the environment in which we live

rather than changes in our genetic endowment. In thinking

about the environmental variables that are probably responsi-ble

for the " obesity epidemic, " most of the attention has fo-cused

on the status and cost of the food supply, the compo-sition

of the food that we ingest, and our capacity for or

avoidance of physical exertion. Is it possible that we have

missed other environmental variables that have a capacity to

modify appetite and energy balance? In this issue, Spiegel and

colleagues (2) present experimental results suggesting that in-

creasing

sleep deficits (or debts), perhaps a result of our hectic

lifestyles, bring about physiologic changes in the hormonal

signals that promote hunger and, perhaps thereby, obesity.

To address this question, Spiegel and colleagues con-ducted

a randomized, 2-period, 2-condition crossover clin-ical

study in which 12 healthy men were studied after 2

days of sleep restriction or sleep extension under conditions

of controlled caloric intake and physical activity. The mea-surements

made in the period after altered sleep included

the hormones leptin and ghrelin and an assessment of hun-ger

and appetite. The findings were straightforward. De-spite

unchanged body weights and energy supply provided

by intravenous infusion of glucose, the period of sleep curtail-ment

was associated with reduced levels of the fat-derived

hormone leptin and increased levels of the stomach-derived

hormone ghrelin. Both of these changes should increase hun-ger.

Of note, the authors' behavioral assay detected these ex-pected

effects because increased sleep debt increased a semi-quantitative

measure of hunger. The correlation between the

increase in appetite and the increased ratio of ghrelin to leptin

was even more impressive. Thus, in this paradigm, sleep cur-tailment

for 2 days entrains a change in 2 peripheral hor-mones.

From our previous knowledge of the effects of these

hormones, we would predict that the sleep-related changes

would stimulate hunger and, possibly, weight gain.

Although the results are provocative, several key ques-tions

remain. First, it remains to be determined how

closely the hormonal consequences of the authors' experi-mental

model for sleep curtailment will predict the conse-quences

of altered sleep that occur in the population at

large. Second, although the altered levels of leptin and

ghrelin are in the right direction to stimulate hunger and

their ratio correlates with hunger measurements, the rela-tionship

is an association rather than causal in nature. We

need interventional studies to clarify the biological signifi-cance

of the changes. Third, factors apart from leptin and

ghrelin might be involved in changing appetite during

sleep curtailment. For example, cortisol, which may be ris-ing

because of the stress of sleep curtailment or other un-known

factors, might be the true cause of increased hun-ger.

Finally, this study does little to clarify the potential

mechanism linking sleep curtailment to changes in plasma

levels and, possibly, secretion of leptin and ghrelin. An

attractive possibility might be via changes in hypothalamic

control of autonomic nervous system activity, including

changes in the balance of cholinergic (parasympathetic)

and sympathetic tone, which have been shown to influence

secretion of leptin and ghrelin (3, 4).

In addition to sleep curtailment affecting appetite (and

possibly body weight) via the intervention of leptin and

ghrelin, it is worth considering another connection be-tween

the 2 fundamental systems controlling sleep and

body weight regulation. Both systems involve neural cir-cuits

that have input from hypothalamic centers and en-gage

neuropeptides and receptors that have critical roles in

homeostasis. The best illustration involves the neuropep-tide

orexin, which is expressed in neurons with cell bodies

in the lateral hypothalamus, an area classically known as a

" feeding center " (5). Orexin was discovered as a peptide (or

1 of 2 peptides) that evoked feeding behavior in animals

after injection into the brain (6). Remarkably, disruption

of the orexin system is a major cause of narcolepsy in both

animals and humans (7, 8). This example shows that sleep

and body weight are homeostatic responses that may be

controlled by intersecting and overlapping mechanisms.

Spiegel and colleagues' findings raise much food for

thought (so to speak). If the findings prove to be reproduc-ible

and generalizable, and the hormonal changes of leptin

and ghrelin due to sleep curtailment cause changes in food

intake over time, we might add sleep duration to the envi-ronmental

factors that are prevalent in our society and that

contribute to weight gain and obesity. Should we design

controlled studies to measure the effect of sleep-promoting

interventions on appetite and body weight, just as we now

prescribe reduced-calorie diets and exercise? Although rec-

ommendations

to get both a better night's sleep and more

exercise might superficially seem to be at odds with each

other from the perspective of energy expenditure and en-ergy

balance, these simple goals may well become a part of

our future approach to combating obesity.

References

1. Flier JS. Obesity wars: molecular progress confronts an expanding

epidemic.

Cell. 2004;116:337-50. [PMID: 14744442]

2. Spiegel K, Tasali E, Penev P, Van Cauter E. Brief communication:

sleep

curtailment in healthy young men is associated with decreased leptin

levels, 3. DL, Grill HJ, Cummings DE, Kaplan JM. Vagotomy

dissociates

short- and long-term controls of circulating ghrelin. Endocrinology.

2003;144:

5184-7. [PMID: 14525914]

4. Mantzoros CS, Qu D, Frederich RC, Susulic VS, Lowell BB, Maratos-

Flier

E, et al. Activation of beta(3) adrenergic receptors suppresses

leptin _expression

and mediates a leptin-independent inhibition of food intake in mice.

Diabetes.

1996;45:909-14. [PMID: 8666142]

5. Saper CB, Chou TC, Elmquist JK. The need to feed: homeostatic and

hedo-nic

control of eating. Neuron. 2002;36:199-211. [PMID: 12383777]

6. Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H,

et

al. Orexins and orexin receptors: a family of hypothalamic

neuropeptides and G

protein-coupled receptors that regulate feeding behavior. Cell.

1998;92:573-85.

[PMID: 9491897]

7. Mignot E. Sleep, sleep disorders and hypocretin (orexin). Sleep

Med. 2004;5

Suppl 1:S2-8. [PMID: 15301991]

8. Chemelli RM, Willie JT, Sinton CM, Elmquist JK, Scammell T, Lee C,

et

al. Narcolepsy in orexin knockout mice: molecular genetics of sleep

regulation.

Editorial A Good Night's Sleep

Brief Communication: Sleep Curtailment in Healthy Young Men Is

Associated

with Decreased Leptin Levels, Elevated Ghrelin Levels, and Increased

Hunger

and Appetite

Karine Spiegel, Esra Tasali, Plamen Penev, and Eve Van Cauter

Ann Intern Med 2004;141 846-850

Sleep-deprived healthy persons experience increased hunger.

They also have increased blood levels of leptin and decreased

levels of ghrelin (hormones that regulate satiety and hunger).

These hormonal effects could be the cause of their increased

hunger.

Context

Studies in animals and humans suggest that sleep duration

is an important regulator of metabolism.

Contribution

In this study, 12 young, healthy, normal-weight men ex-hibited

reductions in the satiety hormone leptin, increases

in the hunger hormone ghrelin, and increases in hunger

after 2 nights of only 4 hours of sleep compared with af-ter

2 nights of 10 hours of sleep.

Implications

Inadequate sleep seems to influence the hormones that

regulate satiety and hunger in a way that could promote

excess eating.

–The Editors

pdf >

Background: Total sleep deprivation in rodents and in humans

has been associated with hyperphagia. Over the past 40 years,

self-reported sleep duration in the United States has decreased by

almost 2 hours.

Objective: To determine whether partial sleep curtailment, an

increasingly prevalent behavior, alters appetite regulation.

Design: Randomized, 2-period, 2-condition crossover clinical

study.

Setting: Clinical Research Center, University of Chicago, Chi-cago,

Illinois.

Patients: 12 healthy men (mean age [±SD], 22 ± 2 years; mean

body mass index [±SD], 23.6 ± 2.0 kg/m 2 ).

Measurements: Daytime profiles of plasma leptin and ghrelin

levels and subjective ratings of hunger and appetite.

Intervention: 2 days of sleep restriction and 2 days of sleep

extension under controlled conditions of caloric intake and phys-ical

activity.

Results: Sleep restriction was associated with average reductions

in the anorexigenic hormone leptin (decrease, 18%; P 0.04),

elevations in the orexigenic factor ghrelin (increase, 28%; P<

0.04), and increased hunger (increase, 24%; P< 0.01) and appe-tite

(increase, 23%; P 0.01), especially for calorie-dense foods

with high carbohydrate content (increase, 33% to 45%; P

0.02).

Limitations: The study included only 12 young men and did not

measure energy expenditure.

Conclusions: Short sleep duration in young, healthy men is

associated with decreased leptin levels, increased ghrelin levels,

and increased hunger and appetite.

Ann Intern Med. 2004;141:846-850. www.annals.org

For author affiliations, see end of text.

See editorial comment on pp 885-886.

Sleep plays an important role in energy balance. In ro-dents,

food shortage or starvation results in decreased

sleep (1), and, conversely, total sleep deprivation leads to

marked hyperphagia (2). Leptin and ghrelin are peripheral

signals that contribute to the central regulation of food

intake. Leptin, a hormone released by the adipocytes, pro-vides

information about energy status to hypothalamic reg-ulatory

centers (3). In humans, circulating leptin levels rap-idly

decrease or increase in response to acute caloric

shortage or surplus, respectively (4). These changes in lep-tin

levels have been associated with reciprocal changes in

hunger (4). Ghrelin, a peptide produced predominantly by

the stomach, is also involved in energy balance regulation,

but, in contrast to the anorexigenic effects of leptin, ghrelin

stimulates appetite (5). It has been proposed that leptin

and ghrelin " represent the `yin–yang' of one regulatory sys-tem

that has developed to inform the brain about the cur-rent

energy balance state " (6).

Over the past 40 years, sleep duration in the U.S.

population has decreased by 1 to 2 hours (7–10). The

proportion of young adults sleeping fewer than 7 hours per

night has more than doubled between 1960 and 2001–

2002 (from 15.6% to 37.1%) (7–10). The effect of sleep

curtailment on the control of appetite and food intake is

not known. Because of the well-documented associations

between sleep and food intake (1, 2), we sought to deter-mine

whether sleep duration influences the daytime pro-files

of leptin and ghrelin.

METHODS

Participants

Twelve healthy men (mean age [SD], 22 2 years];

mean body mass index [SD], 23.6 2.0 kg/m2) who

did not smoke or take any medications participated in the

study. All of the men were within 10% of ideal body

weight and had regular nocturnal time in bed of 7 to 9

hours. We excluded persons who had traveled across time

zones less than 4 weeks before the study.

..... During the week

preceding each study, we asked participants not to deviate

from a fixed time in bed (11:00 p.m. to 7:00 a.m.) by more

than 30 minutes. Naps were not allowed.

The men participated in 2 studies that were conducted

in a randomized order, were spaced at least 6 weeks apart,

and were performed in the Clinical Research Center at the

University of Chicago, Chicago, Illinois. Six of the 12 men

first performed the study with restricted time in bed, and

the remaining 6 men first performed the study with ex-tended

time in bed. Average weight did not change over

the time period separating the 2 study conditions (75.2 kg

in the sleep restriction condition vs. 75.4 kg in the sleep

extension condition; P 0.2). We obtained blood samples

at 20-minute intervals from 8:00 a.m. to 9:00 p.m. after 2

consecutive nights of 10 hours in bed (10:00 p.m. to 8:00

a.m.; sleep extension) and after 2 consecutive nights of 4

hours in bed (1:00 a.m. to 5:00 a.m.; sleep restriction).

Sleep was recorded every night. For both extension and

restriction conditions, each overnight stay began at 7:00

p.m. with a standard hospital dinner, and the first over-night

stay ended after breakfast, which was served at 8:00

a.m. We instructed the participants not to deviate from

their usual eating habits between breakfast and dinner, but

caloric intake was not otherwise monitored. Participants

were readmitted in the early evening and, after receiving a

standard hospital dinner at 7:00 p.m., remained at bed

rest. At 8:00 a.m. after the second night, the participants'

caloric intake was kept constant to avoid meal-related fluc-tuations

of hunger and satiety and consisted of an intrave-nous

glucose infusion at a constant rate of 5 g/kg of body

weight every 24 hours. There was no other source of calo-ries.

Every hour from 9:00 a.m. to 9:00 p.m., the men

completed validated visual analogue scales (0 to 10 cm) for

hunger (11) and appetite for various food categories (12).

To assess hunger, we asked participants to mark their re-sponse

to the question " How hungry do you feel right

now? " on a 10-cm scale (with " not at all hungry " on the

left and " extremely hungry " on the right). To assess appe-tite,

we asked participants to mark their response to how

much they would enjoy eating foods from 7 different food

categories on a 10-cm scale (with " not at all " on the left

and " very much " on the right). They were asked to provide

a score based only on their appetite at the moment, with-out

concern for calories, fat, or a healthy diet. The food

categories were sweets (such as cake, candy, cookies, ice

cream, and pastry); salty foods (such as chips, salted nuts,

pickles, and olives); starchy foods (such as bread, pasta,

cereal, and potatoes); fruits and fruit juices; vegetables;

meat, poultry, fish, and eggs; and dairy products (such as

milk, cheese, and yogurt).

...

RESULTS

Leptin levels were stable across the daytime period un-der

both sleep conditions, which was consistent with the

fact that calories were exclusively delivered in the form of a

constant glucose infusion. Average total sleep time was 9

hours and 8 minutes when the men spent 10 hours in bed

and 3 hours and 53 minutes when the men spent 4 hours

in bed (P 0.01). When spending 4 hours in bed, the

participants had mean leptin levels that were 18% lower

(2.1 ng/mL vs. 2.6 ng/mL; P 0.04) (Figure 1, part A)

and mean ghrelin levels that were 28% higher (3.3 ng/mL

vs. 2.6 ng/mL; P 0.04) (Figure 1, part than when the

participants spent 10 hours in bed. The ratio of the con-centrations

of orexigenic ghrelin to anorexigenic leptin in-creased

by 71% (CI, 7% to 135%) with 4 hours in bed

compared with 10 hours in bed. Sleep restriction relative to

sleep extension was associated with a 24% increase in hun-ger

ratings on the 10-cm visual analogue scale (P 0.01)

and a 23% increase in appetite ratings for all food catego-ries

combined (P 0.01) (Figure 1, parts C and D, and

Table 1). The increase in appetite tended to be greatest for

calorie-dense foods with high carbohydrate content

(sweets, salty foods, and starchy foods: increase, 33% to

45%; P 0.06) (Table 1). The increase in appetite for

fruits and vegetables was less consistent and of lesser mag-nitude

(increase, 17% to 21%) (Table 1). Appetite for

SUMMARIES FOR PATIENTS

Sleep Duration and Levels of Hormones That Influence Hunger

7 December 2004 | Volume 141 Issue 11 | Page I-52

Summaries for Patients are a service provided by ls to help

patients better understand the complicated and often mystifying

language of modern medicine.

Summaries for Patients are presented for informational purposes only.

These summaries are not a substitute for advice from your own medical

provider. If you have questions about this material, or need medical

advice about your own health or situation, please contact your

physician. The summaries may be reproduced for not-for-profit

educational purposes only. Any other uses must be approved by the

American College of Physicians.

The summary below is from the full report titled " Brief

Communication: Sleep Curtailment in Healthy Young Men Is Associated

with Decreased Leptin Levels, Elevated Ghrelin Levels, and Increased

Hunger and Appetite. " It is in the 7 December 2004 issue of ls of

Internal Medicine (volume 141, pages 846-850). The authors are K.

Spiegel, E. Tasali, P. Penev, and E. Van Cauter.

What is the problem and what is known about it so far?

Hormones are substances in the body that help to regulate body

processes. Over recent years, researchers have been learning a lot

about the hormones that help to regulate hunger. Two of these

hormones are called leptin and ghrelin. Leptin decreases hunger, so

people do not feel hungry when leptin levels are high. Ghrelin

increases hunger, so people feel hungry when ghrelin levels are high.

Sleep plays an important role in the body's use and storage of energy

from food. Researchers have found that lack of sleep leads to hunger

in rodents and, possibly, hunger in humans. It is unknown whether

lack of sleep influences the hormones that help to regulate hunger.

Why did the researchers do this particular study?

To determine whether lack of sleep is associated with changes in the

levels of the hunger hormones leptin and ghrelin.

Who was studied?

12 young, healthy men who all had normal body size, were nonsmokers,

and were receiving no medications.

How was the study done?

The researchers conducted the study in a medical center.

What did the researchers find?

After limited sleep, leptin levels decreased, ghrelin levels

increased, and the men reported increased hunger, especially for

foods with high carbohydrate content.

What were the limitations of the study?

The study included only 12 young, healthy men under strict research

conditions. In addition, the researchers did not measure energy

expenditure, so this study cannot determine whether an increase in

energy expenditure might account for increased hunger after lack of

sleep.

What are the implications of the study?

Lack of sleep seems to influence the levels of hunger-regulating

hormones in such a way that hunger increases. It is possible that

chronic lack of sleep might lead to overeating.

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