(This is a sample cover image for this issue. The actual cover is not yet available at this time.)
This article appeared in a journal published by Elsevier. The attached
copy is furnished to the author for internal non-commercial research
and education use, including for instruction at the authors institution
and sharing with colleagues.
Other uses, including reproduction and distribution, or selling or
licensing copies, or posting to personal, institutional or third party
websites are prohibited.
In most cases authors are permitted to post their version of the
article (e.g. in Word or Tex form) to their personal website or
institutional repository. Authors requiring further information
regarding Elsevier’s archiving and manuscript policies are
encouraged to visit:
Author's personal copy
Leptin concentrations in response to acute stress predict subsequent intake of
A. Janet Tomiyamaa,b,⁎,1, Imke Schamarekc,1, Robert H. Lustigb,d, Clemens Kirschbaumc, Eli Putermane,
Peter J. Havelf, Elissa S. Epelb,e,⁎⁎
aDepartment of Psychology, UCLA, Los Angeles, CA, USA
bCenter for Obesity Assessment, Study, and Treatment, UCSF, San Francisco, CA, USA
cDepartment of Psychology, Dresden University, Dresden, Germany
dDepartment of Pediatrics, UCSF, San Francisco, CA, USA
eDepartment of Psychiatry, UCSF, San Francisco, CA, USA
fDepartment of Molecular Biosciences, School of Veterinary Medicine and Department of Nutrition, UC Davis, CA, USA
a b s t r a c ta r t i c l ei n f o
Received 21 June 2011
Received in revised form 3 April 2012
Accepted 24 April 2012
Available online 2 May 2012
Both animals and humans show a tendency toward eating more “comfort food” (high fat, sweet food) after
acute stress. Such stress eating may be contributing to the obesity epidemic, and it is important to understand
the underlying psychobiological mechanisms. Prior investigations have studied what makes individuals eat
more after stress; this study investigates what might make individuals eat less. Leptin has been shown to
increase following a laboratory stressor, and is known to regulate satiety. This study examined whether
leptin reactivity accounts for individual differences in stress eating. To test this, we exposed forty women
to standardized acute psychological laboratory stress (Trier Social Stress Test) while blood was sampled
repeatedly for measurements of plasma leptin. We then measured food intake after the stressor. Increasing
leptin during the stressor predicted lower intake of comfort food. These initial findings suggest that acute
changes in leptin may be one of the factors modulating down the consumption of comfort food following
© 2012 Elsevier Inc. All rights reserved.
Coincident with increased prevalence and severity of psychological
stress in the general population [1,2], the prevalence of overweight
and obesity has reached epidemic levels . Understanding the con-
nections between stress and obesity are critically important. Psycho-
logical stress is an increasingly well-established factor implicated in
the development of obesity . A key mechanism through which stress
likely leads to weight gain and obesity is stress-induced eating. Stress-
induced eating of palatable foods is conserved across species. Both
humans [5–7] and animals  have been documented to increase
their food intake following stress or negative emotion, even if the
organism is not hungry [9,10]. Further, the type of food eaten tends
to be high in sugar or fat, or both [11–13], commonly referred to as
Various psychological and other factors predispose people to
stress-induced eating. For example, being female, overweight, or
scoring high in dietary restraint (a measure of chronic dieting
attempts) puts one at risk for increased food intake in response to a
psychological laboratory stressor [5,14,15]. As for what physiological
factors underlie stress-induced eating, prior research has focused on
the stress-responsive hypothalamic–pituitary–adrenocortical (HPA)
axis and glucocorticoids. In one study, for example, subjects who
responded with the greatest amount of cortisol in response to a
laboratory stressor, compared to a session with no stressor,
consumed the greatest amount of high fat, sugary food .
Furthermore, glucocorticoid administration studies in humans and
rodents have documented increased food intake as well as a shift in
preference toward sweet and fatty foods [16–18]. Although some
studies suggest that glucocorticoids directly increase preference of
sweet and high fat food [17,18], stress affects the brain and bodily
systems through multiple pathways [12,19,20] and accumulating
evidence exists suggesting the role of other neuropeptide systems in
modulating consumption during stress towards sweet and fatty
Although understanding what triggers increases in eating after
stress is important, it is equally important to understand what
might protect an individual from stress eating. That is, we must also
Physiology & Behavior 107 (2012) 34–39
⁎ Correspondence to: A.J. Tomiyama, 1285 Franz Hall, 502 Portola Plaza, Los
Angeles, CA 90095, USA. Tel.: +310 825 2961.
⁎⁎ Correspondence to: E.S. Epel, 3333 California Street, Suite 465, San Francisco, CA
94118, USA. Tel.: +1 415 476 7648; fax: +1 415 502 1010.
E-mail addresses: email@example.com (A.J. Tomiyama), firstname.lastname@example.org
0031-9384/$ – see front matter © 2012 Elsevier Inc. All rights reserved.
Contents lists available at SciVerse ScienceDirect
Physiology & Behavior
journal homepage: www.elsevier.com/locate/phb
Author's personal copy
identify what physiological factors might underlie lower food
consumption following stress.
One possible modulator of stress eating is leptin, the protein
product of the ob gene [21–23]. Leptin circulates in the bloodstream,
reflects the amount of fat stores, recent energy balance and dietary
macronutrient composition [24–27]. Leptin provides a signal to the
hypothalamus of body fat reserves and recent energy intake
[21–23,28,29], and appears to act as a long-term hormonal signal in
the regulation of energy homeostasis [30–33]. Leptin contributes to
body weight regulation by affecting both feeding behavior and energy
expenditure. In rodents, leptin upregulates thermogenesis in brown
adipose tissue. Leptin also exerts effects within the hypothalamus,
regulating homeostatic food intake [30–32], and in the ventral teg-
mental area, reducing dopamine neurotransmission and extinguishing
the reward value of food . Paradoxically, obese humans tend to
have higher levels of leptin, suggesting a state of leptin resistance
Circulating leptin concentrations increase 4–6 h after meals in
response to nutrient-induced insulin secretion [27,35]. However,
leptin may also be acutely responsive to psychological stress
[12,36]. Brydon et al.  exposed subjects to psychological stress
and measured plasma leptin concentrations at baseline, immediately
after the stressor, and 45 min post-stressor. They found a small but
significant increase of leptin, which peaked at 45 min following
exposure to the stressor and was not correlated with cortisol
response to the same task.
These stress-related changes in leptin may also modulate stress-
induced eating. One study has examined leptin, stress, and eating
together  and reported that higher circulating serum leptin
concentrations over one day were related to less overall food
consumption following stress compared with days on which the
subjects were not exposed to stress. This study suggests that tonic
serum concentrations of leptin may be linked to decreased stress-
A remaining question is whether acute changes in leptin under
conditions of stress might affect subsequent food intake, or acute
stress eating. In the current study, we tested whether leptin
modulates stress eating by exposing women to a standardized
laboratory stressor, discreetly measuring their food choices and
amount eatenfollowingthe stressor,
throughout the stress session. Given the prior research implicating
leptin in decreased food consumption, we hypothesized that leptin
responses to stress would be negatively associated with comfort
food consumption. We also measured cortisol to assess whether
leptin effects were independent of, or associated with, the known
effects of cortisol on stress-induced eating behavior.
2. Materials and methods
Sixty-three healthy, non-smoking, post-menopausal women aged
50 to 80 years were recruited throughout the San Francisco Bay area
through flyers posted within the University of California, San Francisco
(UCSF) campuses and hospitals and the community as well as
advertisements in local newspapers and radio stations. The sample
was homogeneous in terms of being all women, postmenopausal, and
of a limited age range, which reduces variance in these factors which
can alter leptin levels [21,23,28,29,38–41] and eating behavior
[15,42–44]. To capture subjects with a wide range of psychosocial
stress, the sample was comprised of caregivers of family members
with dementia as well as BMI- and age-matched control subjects.
Forty of these subjects took part in the laboratory stress session.
Exclusion criteria also included the presence of metabolic or endocrine
disease such as diabetes, substance abuse, medications known to affect
hormones (e.g. glucocorticoids), current major injuries or illness, and
current bipolar or eating disorders.
All procedures were approved by the UCSF Committee on Human
Research and all subjects provided written informed consent.
Subjects were screened for eligibility over the telephone and in
person. To confirm eligibility, fasting laboratory tests ensured normal
liver, kidney and thyroid function, and glucose levels.
Subjects completed two visits at the UCSF Clinical and Translational
Science Institute Clinical Research Center (CTSI-CRC). They were asked
to refrain from physical activity and consuming alcohol or caffeine after
midnight prior to their first appointment. During the first visit a fasting
blood sample was collected shortly after arrival to assess fasting leptin
levels. All subjects' blood was collected between 0730 h and 0830 h to
minimize any potential impact of the diurnal pattern of leptin .
Body weight, height, and waist and hip circumferences were also
assessed. Subjects were then scheduled to return a week later.
Questionnaires assessing sociodemographic variables and individual
difference measures (see measures below) were handed out to the
subjects to be completed at home and returned during the second visit.
At the second visit, subjects were provided with a standardized
lunch at noon to equalize the amount of food intake prior to the
experimental session. The caloric content of every subject's lunch
was identical and was prepared by the CTSI-CRC metabolic kitchen.
An indwelling forearm catheter was inserted and subjects rested for
1 h, followed by a brief questionnaire during which current negative
affect and current hunger were assessed. Next, a modified Trier Social
Stress Test (TSST)  was used to expose subjects to a standardized
psychosocial stressor and assess circulating leptin responses to stress.
Three blood samples were collected throughout the stress task and
recovery period for measurement of leptin: 0 min (baseline), 50 min
after the onset of the stressor, and 90 min after the onset of the
stressor. Salivary samples to measure cortisol were taken at 0, 15,
20, 30, 50, and 90 min post-stressor onset . All subjects were
tested individually between the hours of 1415 h and 1715 h to limit
the diurnal variation in HPA axis activity and leptin levels.
Immediately following the laboratory stressor, negative affect and
hunger were again assessed. Then subjects were moved to a break
room with a snack buffet for a 30-min period during which food
intake was covertly measured.
2.3. Stress manipulation
The modified TSST was a 50-min session beginning with four
5-min stressful periods (1) introduction to two “trained evaluators”
and receiving instructions for the task, (2) a preparation period in
which subjects were asked to prepare a 5-min speech on their
“personal strengths and weaknesses,” (3) delivering the speech, and
(4) a challenging serial subtraction task. The evaluators were
trained confederates who kept neutral facial expressions during the
task performance and used a set of standardized comments to
increase stress and ensure that each subject experienced the task as
demanding. The tasks were followed by 30 min of sitting quietly.
This test has been shown to reliably result in a short-lived increase
of psychological stress with physiological manifestations (i.e., cortisol
secretion) and has been used in several previous studies examining
the role of stress in eating behavior [9,12].
2.4. Snacking session
During the snacking session (approximately 30 min after the
stress session and 3 h since their last meal) subjects were left alone
in a room with leisure reading material for 30 min and also had access
to an array of snacks from which they could choose and eat as much
A.J. Tomiyama et al. / Physiology & Behavior 107 (2012) 34–39
Author's personal copy
as they wanted. Subjects were not required to but merely invited to
eat, and were not aware that their food intake was being measured.
To assess food choice with regard to sweet, salty, low-fat, and
high-fat foods, four categories of snack choices were presented on a
large platter, without individual packaging (see Table 1). Each serving
of different food items was separately weighed to the nearest 0.1 g
before and after the subject had left the room to assess how much
they consumed. If subjects did not eat the food items in the laboratory
but took them home, their data were not analyzed. This study design
is a common paradigm to assess food choices in humans after
laboratory stressors [10,12,15].
2.5.1. Body mass index (BMI)
Body weight was measured on a digital scale with subjects in light
clothing without shoes. Height was measured to the nearest of 0.1 cm
using a Harpenden stadiometer. BMI was calculated as weight in
kilograms divided by height in meters squared.
Plasma leptin samples during the stressor were obtained from
blood samples collected via the inserted indwelling catheter. Blood
samples were centrifuged, aliquoted and stored in polypropylene
vials at −80 °C until analysis. Samples were assayed with a
radioimmunoassay kit using a125I-human leptin tracer and human
leptin standards from Linco Research, Inc. (St. Charles, MO, USA) in
Dr. Havel's laboratory (UC Davis, CA, USA). The intra- and interassay
variations of the assay were 6.6% and 12.0% respectively. Changes of
circulating leptin during the stress session were calculated according
to the area-under-the-curve with respect to increase (AUCi) formula
according to the recommendations of Pruessner et al.  to calculate
time-dependent leptin secretion. In other words, we examined leptin
secretion over the test period controlling for baseline leptin values,
and label this throughout as “leptin reactivity.”
Salivary cortisol strongly reflects levels of serum cortisol and
indexes the amount of free or biologically viable cortisol . To
collect salivary samples, subjects were asked to drool passively
through a straw into a tube, which then were kept on ice and then
frozen at −20 °C degrees. Samples were sent for batch assay to
Dr. Kirschbaum's laboratory (Dresden, Germany). Salivary cortisol was
assayed with a chemiluminescence immunoassay using a commercial
kit (IBL; Hamburg, Germany). The intra-assay CV was 2.9% for high
and 9.1% for low levels. The sensitivity lower limit was 0.006 μg/dl. As
with leptin, we calculated cortisol secretion during the stress session
Information on age and ethnicity was obtained by self-report from
the subjects. The number of lifetime diets (resulting in at least a five
pound loss of weight) and currently being on a diet (yes/no) were
assessed in the questionnaire packet the participants completed at
home between the first and second visits. Prior to and immediately
after the stressor, ratings of negative affect were obtained as part of
a manipulation check using six negative emotions taken from the
Affect Balance Scale . The items were answered on a 4-point
Likert-type scale with 0=“ not at all” and 4=“a great deal.” A total
score was obtained as sum of the items (Cronbach's α=.79). Ratings
of current subjective feelings of hunger were assessed on a 4-point
Likert-type scale (0=not hungry at all, 4=a great deal), prior to
and after the stressor. To disguise our interest in subjects’ specific
food intake, the item assessing current hunger was interspersed
among the mood ratings.
2.5.5. Food intake
Food intake was quantified as the weight of each food item
consumed in grams. To obtain a measure for each food category, the
sum of the weight of consumed food items within each category was
calculated. Both total consumption and category-specific (i.e. high
fat, high sugar) consumption were used as the primary dependent
Statistical analyses were performed using SPSS for Windows 15.0.
(SPSS Inc., Chicago, IL, USA). Pearson correlation coefficients were
calculated to test the association of outcome variables with potential
confounding variables. Paired sample t-tests were computed to
perform a manipulation check to confirm that the stressor increased
cortisol and ratings of negative affect. The Wilcoxon Ranked Sum
Test was used to test whether subjects´ subjective ratings of hunger
differed significantly pre- and post-stressor. A one-way Repeated
Measure Analysis of Variance was used to investigate whether leptin
levels at each timepoint during the stressor differed significantly
from each other. Partial correlations were calculated to investigate
the relationship between cortisol and leptin reactivity controlling
for potential confounding variables and to determine whether leptin
reactivity significantly predicted the amount of food consumed. All
leptin analyses controlled for BMI.
3.1. Subject characteristics
Forty women completed the laboratory stressor session with
complete leptin data. One subject had a fasting leptin concentration
greater than four standard deviations above the mean and was
excluded from statistical analysis, leaving 39 women. Ten women
did not undergo the eating session, leaving 29 women for whom
complete data were available. The average age was 62 years
(SD=6.33; range: 51–79) and the average BMI was 26.2 and ranged
from lean to obese (SD=5.3; range: 17.7–37.5). In terms of BMI
categories, 3.3% were “underweight,” 40% were “normal” weight,
33.3% were “overweight,” 16.7% were “obese,” and 6.7% were
“morbidly obese.” The majority of subjects self-identified as white
(85%), with the remaining 13% Asian/Pacific Islander/Native American,
and 3% African American.
Food types and amounts served for post-stressor eating behavior.
High fatChocolate chip cookies (114 g)
Chocolate chip ice cream (500 g)
Fruit (grapes, apples) (500 g)
Animal crackers (38 g)
Cheese (cheddar, Swiss, provolone) (80 g)
Potato chips (36 g)
Pretzels (36 g)Low fat
Note: Gram values correspond to two pre-packaged serving sizes of each food category.
A.J. Tomiyama et al. / Physiology & Behavior 107 (2012) 34–39
Author's personal copy
The women in this sample had a mean fasting leptin concentration
of 18.8 ng/ml (SD=14.6; range 2.5–55.0 ng/ml), which is within the
normal physiological range of leptin levels . The majority of the
subjects (82%) reported to not be on a diet currently. Of the
individuals on a diet, 50% were normal weight, 33.3% were
overweight, and 16.7% were obese. The inclusion of caregivers and
control subjects resulted in a moderate range of perceived stress
scores of 0 to 27 out of a maximum of 30. Being a caregiver had no
effect on any of the analyses and thus the two groups were combined.
3.2. Preliminary analyses and manipulation check
Q-Q plots indicated leptin and cortisol values at all time points
were not normally distributed, and this was corrected via a natural
log transformation. As expected, fasting leptin concentrations were
positively correlated with BMI (r=.88, pb.001). No significant
correlation was found between fasting leptin levels and age (r=.16,
p=.32) or current dieting (r=−.05, p=.75).
The stress manipulation was successful—comparison of group
means revealed that salivary cortisol levels increased from baseline,
reached peak levels 30 min after the onset of the stressor and
returned to baseline levels by 90 min after the onset of the stressor.
Further, a t-test showed cortisol levels at peak were significantly
higher than cortisol levels at baseline before the onset of the stressor,
indicating that the stress manipulation elicited the intended stress
reactivity response (t=8.91, pb.001). In addition, subjects reported
a significant increase in negative affect from baseline to the post-
stress session (t=7.30, pb.001) (see Table 2).
3.3. Food intake
Characteristics of the distribution of food intake measures are
summarized in Table 3. In general, subjects ate more sweet food
than salty food (78% vs. 22%), and more high fat sweet food (34%)
than high fat salty food (17%); while few ate low fat salty food (4%;
see Table 3 for details). Hunger ratings at baseline (before the
stressor) did not correlate with any measures of type or quantity of
food intake (all p>.05). This lack of correlation, and that each subject
ate a standardized meal before the stressor, suggests that the
snacking was non-homeostatic—not related to caloric deprivation.
Hunger ratings remained stable during stress (no changes from pre
to post-stress task, U=0.00, p=.99).
3.4. Leptin during stress
Characteristics of the distribution of circulating leptin concentrations
during the stressor and during recovery are displayed in Table 2.
We first examined the relationship of leptin during stress to
potential confounding variables including fasting plasma leptin
concentrations, BMI, age, current dieting, and baseline hunger ratings.
Leptin levels at all three time points (baseline, 50 min, and 90 min
post-stressor) during the stressor were significantly correlated with
fasting leptin concentrations (r=.96, .98. and .97, respectively, all
pb.001), and BMI (r=.86, .85, and .85, respectively, all pb.001). No
significant correlation was found between age, current dieting and
baseline hunger ratings and leptin levels at all three time points (all
Across the entire sample, there were mean increases of leptin
concentrations from baseline to 50 min post-stressor onset (M=0.30,
SD=1.64) and from 50 min to 90 min post-stressor onset (M=0.40,
SD=1.80). However, neither of these increases was statistically
significant (p>.05). Subjects showed great variation in leptin reactivity
post-stress, ranging from −5.48 to +4.30 ng/ml. Leptin reactivity was
not significantly correlated with cortisol reactivity controlling for the
potential confounding variables, BMI and age (all p>.05). Further,
leptin reactivity was not significantly correlated with BMI, fasting
leptin levels, age, baseline hunger ratings or current dieting (all
3.5. Leptin reactivity during stress session and intake of high fat/high
Next we tested whether leptin reactivity was related to less intake
of high fat/high sugar “comfort” foods. The average AUCi of natural-
logged leptin was 1.05 (SD=5.55) and ranged from −13.99 to
12.51. Leptin reactivity across the test session was negatively related
to high fat sweet food intake (r=−.40, pb.05). Leptin reactivity was
not related to intake in any of the other food categories (see Table 4).
3.6. Leptin reactivity and individual differences in stress and dieting
Because leptin reactivity was related to consumption of high fat/
high sugar foods, we conducted analyses to examine factors that
might potentially contribute to individual differences in leptin
reactivity. Specifically, we examined leptin reactivity in relation to
two variables that, based on prior literature, might contribute to
differences in leptin reactivity: the perceived stressfulness of the
task  and the number of episodes of dieting the participants
engaged in throughoutadulthood
responses during nor after stress were significantly associated with
these variables (all p>.05).
Stress-induced eating behavior likely plays an important role in
current obesity epidemic.
physiological mechanisms are largely unknown, preliminary initial
evidence implicates leptin in the phenomenon of stress-induced
Descriptive statistics of Physiological and psychological changes during lab stressor.
Subjective hunger ratings
Characteristics of distribution of food intake during the snacking session.
Food type consumed (g)Mean SDMinMax% eaten
Total amount of food eaten
High fat sweet food
Low fat sweet food
High fat salty
Low fat salty
A.J. Tomiyama et al. / Physiology & Behavior 107 (2012) 34–39
Author's personal copy
eating . The present study investigated whether leptin may be
one of the physiological factors that modulate stress-induced eating
behavior, which is the characteristic shift in food preference towards
high fat and high sugar foods following exposure to stress. We found
that leptin increases from baseline in response to acute stress were
significantly related to lower consumption of high fat, sweet foods
—“comfort” foods. This association between leptin reactivity and
subsequent food intake appeared to be specific for high fat sweet
food intake and no significant relationship was found between leptin
reactivity and any other food category. However, we note that there
was a smaller marginal relationship between leptin reactivity with
greater intake of low fat sweet food, and the potential distinction
between the two patterns should be re-examined in replicative
research. Studies on leptin and salty food consumption is scarce.
Our findings appear in line with results reported by Kawai and
colleagues  who administered leptin into lean mice and found
changes in taste nerve responses to sweet but not sour, salty, or bitter
substances. More work needs to be done to delineate the effects of
leptin on non-sweet substances. However, in studies of rodents 
and humans [12,13], stress appears to predominantly affect sweet
food intake (rather than chow or salty foods, respectively). Sweet in
the presence of high fat may be a particularly relevant outcome
measure in this specific context of stress eating.
Moreover, in the present study morning fasting leptin levels did not
predict food intake following the stressor, underscoring the relevance
of leptin reactivity as a novel correlate and potentially important
predictor of stress eating, especially since this marker was found to
be independent of BMI and fasting leptin concentrations.
Our result differs from the pattern of findings reported by
Appelhans , who found that higher daily leptin concentrations
were related to less total food consumption following stress but not
sweet high fat food intake specifically as found in the present study.
This may have been a consequence of the different leptin measures
the two studies used. Rather than measuring diurnal circulating
leptin values, we used leptin measures during stress, again
emphasizing leptin reactivity as a potentially more relevant marker
implicated in stress eating. As leptin is an energy homeostatic
hormone that reduces food intake by acting centrally within the
hypothalamus and the ventral tegmental area, extinguishing the
reward value of food, less high fat, sweet food intake following an
acute increase in leptin during stressful periods in the present study
might be a consequence of a dampened comforting effect of these
foods in stressful situations [30,31,51].
At the group level, exposure to the psychological laboratory
stressor did not significantly increase mean leptin levels during or
after the stressor. This is in contrast with Brydon et al.  who,
with a larger sample, reported a small but significant increase in
leptin levels following a similar laboratory psychosocial stressor.
Our inability to replicate these findings may in part be due to a
smaller sample size and a higher average age of the participants in
the present study, or the wide range of leptin responses in our
study, with half of the participants showing an increase of leptin
during stress and others showing a decrease in leptin levels during
stress. Our study suggests that a pattern whereby leptin does not
increase during stress may lead to greater high fat, sweet food intake,
and this underscores the importance of further studying the factors
that determine whether leptin increases or decreases acutely
following stress. In this initial study, we appear to have ruled out
the perceived stressfulness of the task and the number of episodes
of previous dieting as possible influencing variables predicting acute
leptin changes during stress.
There was no correlation between leptin and cortisol reactivity,
which is in line with findings of by Brydon et al. . Cortisol (in
combination with insulin) has been implicated in prior studies of
stress eating  but our data suggest that any leptin effect on food
intake may be an independent process that is not driven by cortisol.
This could be even more precisely pinpointed in future studies by
examining stressors that do not engage the HPA axis, such as noise
exposure , and linking leptin changes to eating without any
concomitant increases of cortisol.
A number of limitations of our findings warrant mention. As this
study was conducted solely in postmenopausal women and in a
laboratory setting, these results cannot readily be generalized to
other populations or to other less-controlled situations. Moreover,
our sample was small, which reduced both our power and
generalizability. We cannot rule out the possibility that subjects
may have been aware that their food intake was being monitored.
We demonstrate correlation, which does not infer directionality or
mechanism. This study did not include an unstressed control group,
which leaves the possibility that the reported pattern of leptin change
is unrelated to stress and may have occurred under restful conditions
over the afternoon in some subjects. Further, our inter-assay variation
was larger than our observed effect (12%), suggesting that future
studies should examine changes of circulating leptin in response to
acute stress and compare them with leptin responses during a control
session on a separate day to rule out that the observed pattern
occurred by chance. We did not have measures of sympathetic
nervous system (SNS) activity in this study. The SNS is activated by
stress and is a regulator of leptin production  (and vice-versa;
leptin is a potent stimulator of the SNS ), and future studies are
needed to determine whether the SNS might drive or modulate the
effects seen here. Ghrelin, a peptide that has been shown recently
to mediate stress eating in mice , similarly was not measured,
and might also be a key component driving stress eating, either
alone or in concert with leptin, in humans.
This study is significant in that it documented the heterogeneity of
leptin responses to acute stress. Increases of circulating leptin
concentrations during a psychological laboratory stress task predicted
less consumption of high fat, high sugar foods but not other types of
foods. This suggests that leptin reactivity may be implicated in
reducing stress-induced eating behavior. The relationship between
leptin activity and stress-induced eating behavior appear to be
independent of cortisol reactivity.
We speculate that leptin may be acting as a modulator of stress
eating. When an individual has an adaptable, flexible allostatic stress
response that is sensitive enough to upregulate leptin secretion in
response to stress, that individual may not fall prey to the drive to
consume comfort food. When the system does not respond, meaning
that leptin reactivity is low or absent, comfort food eating may be
more easily triggered. In sum, this study implicates circulating leptin
reactivity in potentially dampening the known shift in food preference
to high fat, sweet food following exposure to stress, and points towards
its potential as an independent modulator of stress eating. Leptin
responses to acute stress show a complex pattern, of which the exact
nature, cause and underlying mechanisms remain to be determined.
The authors gratefully acknowledge support from the Anthony
Marchionne Foundation, the Robert Wood Johnson Foundation
Correlations between grams of food eaten of each food category and leptin reactivity.
High fat sweet
Low fat sweet
High fat salty
Low fat salty
A.J. Tomiyama et al. / Physiology & Behavior 107 (2012) 34–39
Author's personal copy Download full-text
Health and Society Scholars Program, and National Institute of Mental
Health Award K08 MH64110-01A1. All funding sources had no
further role in study design; in the collection, analysis and
interpretation of data; in the writing of the report; and in the decision
to submit the paper for publication.
 Kudielka BM, Wust S. Human models in acute and chronic stress: assessing
determinants of individual hypothalamus–pituitary–adrenal axis activity and
reactivity. Stress 2010;13:1–14.
 American Psychological Association. Stress in America. Washington, DC: American
Psychological Association; 2009.
 Centers for Disease Control and Prevention. National Health and Nutrition
Examination Survey Data. Hyattsville, MD: National Center for Health Statistics;
 Dallman MF. Stress-induced obesity and the emotional nervous system. Trends
Endocrinol Metab 2010;21:159–65.
 Greeno CG, Wing RR. Stress-induced eating. Psychol Bull 1994;115:444–64.
 Torres SJ, Nowson CA. Relationship between stress, eating behavior, and obesity.
 Adam TC, Epel ES. Stress, eating and the reward system. Physiol Behav 2007;91:
 Dallman MF, Pecoraro N, Akana SF, La Fleur SE, Gomez F, Houshyar H, et al.
Chronic stress and obesity: a new view of "comfort food". Proc Natl Acad Sci U S A
 Appelhans BM, Pagoto SL, Peters EN, Spring BJ. HPA axis response to stress
predicts short-term snack intake in obese women. Appetite 2010;54:217–20.
 Oliver G, Wardle J, Gibson EL. Stress and food choice: a laboratory study.
Psychosom Med 2000;62:853–65.
 Pecoraro N, Reyes F, Gomez F, Bhargava A, Dallman MF. Chronic stress promotes
palatable feeding, which reduces signs of stress: feedforward and feedback effects
of chronic stress. Endocrinology 2004;145:3754–62.
 Epel E, Lapidus R, McEwen B, Brownell K. Stress may add bite to appetite in
women: a laboratory study of stress-induced cortisol and eating behavior.
 Habhab S, Sheldon JP, Loeb RC. The relationship between stress, dietary restraint,
and food preferences in women. Appetite 2009;52:437–44.
 Wardle J, Steptoe A, Oliver G, Lipsey Z. Stress, dietary restraint and food intake.
J Psychosom Res 2000;48:195–202.
 Grunberg NE, Straub RO. The role of gender and taste class in the effects of stress
on eating. Health Psychol 1992;11:97–100.
 Dallman MF, la Fleur SE, Pecoraro NC, Gomez F, Houshyar H, Akana SF.
Minireview: glucocorticoids—food intake, abdominal obesity, and wealthy
nations in 2004. Endocrinology 2004;145:2633–8.
 Freedman MR, Horwitz BA, Stern JS. Effect of adrenalectomy and glucocorticoid
replacement on development of obesity. Am J Physiol 1986;250:R595–607.
 Tataranni PA, Larson D, Snitker S, Young J, Flatt J, Ravussin E. Effects of
glucocorticoid on energy metabolism and food intake in humans. Am J Physiol
 Brydon L, Wright CE, O'Donnell K, Zachary I, Wardle J, Steptoe A. Stress-induced
cytokine responses and central adiposity in young women. Int J Obes (Lond)
 Zukowska-Grojec Z. Neuropeptide Y; a novel sympathetic stress hormone and
more. Ann N Y Acad Sci 1995;771:219–33.
 Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, et al.
Serum immunoreactive-leptin concentrations in normal-weight and obese
humans. N Engl J Med 1996;334:292–5.
 Frederich RC, Hamann A, Anderson S, Lollmann B, Lowell BB, Flier JS. Leptin levels
reflect body lipid content in mice: evidence for diet-induced resistance to leptin
action. Nat Med 1995;1:1311–4.
 Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional
cloning of the mouse obese gene and its human homologue. Nature 1994;372:
 Casanueva FF, Dieguez C. Neuroendocrine regulation and actions of leptin. Front
 Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals.
 Flier JS. Obesity wars: molecular progress confronts an expanding epidemic. Cell
 Havel PJ. Update on adipocyte hormones: regulation of energy balance and
carbohydrate/lipid metabolism. Diabetes 2004;53(Suppl. 1):S143–51.
 Lustig RH. The neuroendocrinology of obesity. Endocrinol Metab Clin North Am
 Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, et al. Leptin levels in
human and rodent: measurement of plasma leptin and ob RNA in obese and
weight-reduced subjects. Nat Med 1995;1:1155–61.
 Jeanrenaud B, Rohner-Jeanrenaud F. Effects of neuropeptides and leptin on
nutrient partitioning: dysregulations in obesity. Annu Rev Med 2001;52:339–51.
 Myers MG, Cowley MA, Munzberg H. Mechanisms of leptin action and leptin
resistance. Annu Rev Physiol 2008;70:537–56.
 Sahu A. Minireview: A hypothalamic role in energy balance with special emphasis
on leptin. Endocrinology 2004;145:2613–20.
 Havel PJ, Bremer AA. Endocrine regulation of energy homeostasis: implcations for
obesity and diabetes. In: Serrano-Rios M, Ordovas JM, Gutierrez-Fuentes JA,
editors. Obesity. Barcelona: Elsevier; 2010. p. 107–25.
 Hommel JD, Trinko R, Sears RM, Georgescu D, Liu ZW, Gao XB, et al. Leptin
receptor signaling in midbrain dopamine neurons regulates feeding. Neuron
 Havel PJ, Townsend R, Chaump L, Teff K. High-fat meals reduce 24-h circulating
leptin concentrations in women. Diabetes 1999;48:334–41.
 Bjorntorp P. Do stress reactions cause abdominal obesity and comorbidities? Obes
 Appelhans BM. Circulating leptin moderates the effect of stress on snack intake
independent of body mass. Eat Behav 2010;11:152–5.
 Cella F, Giordano G, Cordera R. Serum leptin concentrations during the menstrual
cycle in normal-weight women: effects of an oral triphasic estrogen-progestin
medication. Eur J Endocrinol 2000;142:174–8.
 Considine RV. Regulation of leptin production. Rev Endocr Metab Disord 2001;2:
 Pasquali R, Vicennati V, Cacciari M, Pagotto U. The hypothalamic–pituitary–
adrenal axis activity in obesity and the metabolic syndrome. Ann N Y Acad Sci
 Ruhl CE, Everhart JE. Leptin concentrations in the United States: relations with
demographic and anthropometric measures. Am J Clin Nutr 2001;74:295–301.
 Greeno C, Wing R. Stress-induced eating. Psychol Bull 1994;115:444–64.
 Van Strien T, Cleven A, Schippers G. Restraint, tendency toward overeating and ice
cream consumption. Int J Eat Disord 2000;28:333–8.
 Zellner DA, Loaiza S, Gonzalez Z, Pita J, Morales J, Pecora D, et al. Food selection
changes under stress. Physiol Behav 2006;87:789–93.
 Licinio J, Mantzoros C, Negrao AB, Cizza G, Wong ML, Bongiorno PB, et al. Human
 Kirschbaum C, Pirke K, Hellhammer D. The “Trier Social Stress Test”—a tool for inves-
tigating psychobiological stress responses in a laboratory setting. Neuropsychobiology
 Pruessner J, Kirschbaum C, Meinlschmidt G, Hellhammer DH. Two formulas for
computation of the area under the curve represent measures of total hormone con-
centration versus time-dependent change. Psychoneuroendocrinology 2003;28:
 Kirschbaum C, Hellhammer DH. Salivary cortisol in psychobiological research: an
overview. Neuropsychobiology 1989;22:150–69.
 Derogatis LR. Affects balance scale. Baltimore, MD: Clinical Psychometric
 Ahima RS, Flier JS. Leptin. Annu Rev Physiol 2000;62:413–37.
 Sahu A. Leptin signaling in the hypothalamus: emphasis on energy homeostasis
and leptin resistance. Front Neuroendocrinol 2004;24:225–53.
 Kawai K, Sugimoto K, Nakashima K, Miura H, Ninomiya Y. Leptin as a modulator of
sweet taste sensitivities in mice. Proc Natl Acad Sci U S A 2000;97:11044–9.
 Dallman MF, Pecoraro NC, la Fleur SE. Chronic stress and comfort foods:
self-medication and abdominal obesity. Brain Behav Immun 2005;19:275–80.
 Dickerson SS, Kemeny ME. Acute stressors and cortisol responses: a theoretical
integration and synthesis of laboratory research. Psychol Bull 2004;130:355–91.
 Rayner DV, Trayhurn P. Regulation of leptin production: sympathetic nervous
system interactions. J Mol Med 2001;79:8–20.
 Mark AL, Rahmouni K, Correia M, Haynes WG. A leptin-sympathetic-leptin
feedback loop: potential implications for regulation of arterial pressure and
body fat. Acta Physiol Scand 2003;177:345–9.
 Chuang JC, Perello M, Sakata I, Osborne-Lawrence S, Savitt JM, Lutter M, et al.
Ghrelin mediates stress-induced food-reward behavior in mice. J Clin Invest
A.J. Tomiyama et al. / Physiology & Behavior 107 (2012) 34–39