Psychosocial stress induces hyperphagia

and exacerbates diet-induced insulin

resistance and the manifestations of the
Metabolic Syndrome
Valentina Sanghez
,
Maria Razzoli
,
Stefania Carobbio
,
Mark Campbell
,
Jacob McCallum
,
Cheryl Cero
,
Graziano Ceresini
,
Aderville Cabassi
,
Paolo Govoni
,
Paolo Franceschini
,
Valentina de Santis
,
Allison Gurney
,
Ivana Ninkovic
,
Stefano Parmigiani
,
Paola Palanza
,
Antonio Vidal-Puig
,
Alessandro Bartolomucci
Received: March 14, 2013; Received in revised form: July 31, 2013; Accepted: July 31,
2013; Published Online: September 23, 2013
DOI: http://dx.doi.org/10.1016/j.psyneuen.2013.07.022

Abstract

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Summary
Stress and hypercaloric food are recognized risk factors for obesity, Metabolic Syndrome
(MetS) and Type 2 Diabetes (T2D). Given the complexity of these metabolic processes and
the unavailability of animal models, there is poor understanding of their underlying
mechanisms. We established a model of chronic psychosocial stress in which subordinate
mice are vulnerable to weight gain while dominant mice are resilient. Subordinate mice fed
a standard diet showed marked hyperphagia, high leptin, low adiponectin, and
dyslipidemia. Despite these molecular signatures of MetS and T2D, subordinate mice fed a
standard diet were still euglycemic. We hypothesized that stress predisposes subordinate
mice to develop T2D when synergizing with other risk factors. High fat diet aggravated
dyslipidemia and the MetS thus causing a pre-diabetes-like state in subordinate mice.
Contrary to subordinates, dominant mice were fully protected from stress-induced
metabolic disorders when fed both a standard- and a high fat-diet. Dominant mice showed a
hyperphagic response that was similar to subordinate but, unlike subordinates, showed a
significant increase in VO2, VCO2, and respiratory exchange ratio when compared to
control mice. Overall, we demonstrated a robust stress- and social status-dependent effect
on the development of MetS and T2D and provided insights on the physiological
mechanisms. Our results are reminiscent of the effect of the individual socioeconomic
status on human health and provide an animal model to study the underlying molecular
mechanisms.
Chronic stress, metabolism, and metabolic syndrome
September 2011, Vol. 14, No. 5 , Pages 468-474 (doi:10.3109/10253890.2011.606341)

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K. L. Tamashiro, R. R. Sakai, C. A. Shively, I. N. Karatsoreos, and L. P. Reagan

Department of Psychiatry & Behavioral Sciences, Johns Hopkins University School of

Medicine,
Baltimore, MD
, USA
2
Department of Psychiatry & Behavioral Neurosciences, University of Cincinnati College
of Medicine,
Cincinnati, OH
, USA
3
Department of Pathology/Comparative Medicine, Wake Forest University Primate Center,
Winston-Salem, NC
, USA
4
Laboratory of Neuroendocrinology, Rockefeller University,
New York, NY
, USA
5
Department of Pharmacology, Physiology and Neuroscience, University of South Carolina
School of Medicine,
Columbia, SC
, USA
Correspondence: K. L. Tamashiro, Department of Psychiatry & Behavioral Sciences, Johns
Hopkins University School of Medicine, 720 Rutland Avenue, Ross 618, Baltimore, MD
21205, USA. Tel:
410 955 2996. Fax: 410 502 3769. E-mail:
ktamashiro@jhmi.edu

The prevalence of obesity has rapidly escalated and now represents a major public health
concern. Although genetic associations with obesity and related metabolic disorders such as
diabetes and cardiovascular disease have been identified, together they account for a small
proportion of the incidence of disease. Environmental influences such as chronic stress,
behavioral and metabolic disturbances, dietary deficiency, and infection have now emerged
as contributors to the development of metabolic disease. Although epidemiological data
suggest strong associations between chronic stress exposure and metabolic disease, the
etiological mechanisms responsible remain unclear. Mechanistic studies of the influence of
chronic social stress are now being conducted in both rodent and nonhuman primate
models, and phenotypic results are consistent with those in humans. The advantage of these
models is that potential neural mechanisms may be examined and interventions to treat or
prevent disease may be developed and tested. Further, circadian disruption and metabolic
conditions such as diabetes mellitus could increase susceptibility to other stressors or serve
as a stressor itself. Here, we review data from leading investigators discussing the
interrelationship between chronic stress and development of metabolic disorders.

Read More: http://informahealthcare.com/doi/abs/10.3109/10253890.2011.606341

Adherence to the Mediterranean diet and risk of metabolic syndrome and its
components
N. Babio
,
M. Bull
,
J. Basora
,
M.A. Martnez-Gonzlez
,
J. Fernndez-Ballart
,
F. Mrquez-Sandoval
,
C. Molina
,
J. Salas-Salvad
,
on behalf of the Nureta-PREDIMED investigators
Received: July 28, 2008; Received in revised form: October 24, 2008; Accepted:
October 29, 2008; Published Online: January 28, 2009
DOI: http://dx.doi.org/10.1016/j.numecd.2008.10.007

Abstract

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Abstract
Background and aims

The role of diet in the aetiology of metabolic syndrome (MetS) is not well understood. The
aim of the present study was to evaluate the relationship between adherence to the
Mediterranean diet (MedDiet) and MetS.
Methods and results

A cross-sectional study was conducted with 808 high cardiovascular risk participants of the
Reus PREDIMED Centre. MetS was defined by the updated National Cholesterol and
Education Program Adult Treatment Panel III criteria.
An inverse association between quartiles of adherence to the MedDiet (14-point score) and
the prevalence of MetS (P for trend<0.001) was observed. After adjusting for age, sex,
total energy intake, smoking status and physical activity, participants with the highest score
of adherence to the MedDiet (9 points) had the lowest odds ratio of having MetS (OR
[95% CI] of 0.44 [0.270.70]) compared to those in the lowest quartile.
Participants with the highest MedDiet adherence had 47 and 54% lower odds of having low
HDL-c and hypertriglyceridemia MetS criteria, respectively, than those in the lowest
quartile. Some components of the MedDiet, such as olive oil, legumes and red wine were
associated with lower prevalence of MetS.
Conclusion

Higher adherence to a Mediterranean diet is associated with a significantly lower odds ratio
of having MetS in a population with a high risk of cardiovascular disease.
PO14 Activit physique, sdentarit et facteurs alimentaires en relation avec le
syndrome mtabolique

A. Wagner1,

D. Arveiler1,

J. Dallongeville2,

V. Bongard3,

D. Cottel2,

J. Ferrires3,

B. Haas1,

C. Simon4

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DOI: 10.1016/S1262-3636(10)70120-8
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Introduction

Lactivit physique et la sdentarit sont deux concepts diffrents susceptibles dinfluer sur
le profil mtabolique. Ce travail vise valuer leurs associations conjointes avec le
syndrome mtabolique, en tenant compte de lalimentation, partir dune tude
transversale en population gnrale.
Matriels et Mthodes

Les participants sont des habitants de la communaut urbaine de Lille et des dpartements
du Bas-Rhin et de la Haute-Garonne tirs au sort sur les listes lectorales aprs stratification
sur le sexe, lge et la taille de la commune. Les mesures (pression artrielle, tour de taille)
ont t standardises, les examens biologiques centraliss. Les donnes socioconomiques,
comportementales et mdicales ont t collectes par interview. Lactivit physique a t
value avec le questionnaire MOSPA, la sdentarit par le nombre dheures passes assis
par jour. Une enqute alimentaire prospective sur trois jours a permis de dfinir, par analyse
factorielle en composantes principales, un profil alimentaire de type riche et un autre de
type snack et pratique .
Rsultats

De 2005 2007, 3 620 sujets de 35 64 ans ont t recruts (ge moyen : 50,6 ans, 50,3 %
dhommes). Le syndrome mtabolique (dfinition rvise NCEP ATP III) est prsent chez
23,6 % des hommes et 15,9 % des femmes et augmente avec lge dans les 2 sexes. Dans

un modle logistique multivari ajust (rgion, ge, sexe, niveau dtudes, tabagisme,
dpense nergtique au travail, apport calorique total, profils alimentaires), lodds davoir
un syndrome mtabolique augmente avec les quartiles de temps pass assis (OR du quartile
4 compar au 1 : 1,73 [1,282,34]; p de tendance < 10-4) et diminue avec les quartiles de
dpense nergtique de loisirs (OR du quartile 4 compar au 1 : 0,48 [0,360,64]; p de
tendance < 10-4), sans interaction. La dpense nergtique au travail nest pas associe au
syndrome mtabolique. Le profil alimentation riche est associ positivement au
syndrome mtabolique (OR du quartile 4 compar au 1 : 2,33 [1,713,16]; p de tendance
<10-4).
Conclusion

Lactivit physique de loisirs, la sdentarit et une alimentation riche sont associes

indpendamment au syndrome mtabolique chez des adultes dge moyen.
Fetal origins of insulin resistance and the metabolic syndrome: A key role for
adipose tissue?
Contribution de lenvironnement intra-utrin au dveloppement de
linsulinorsistance et du syndrome mtabolique lge adulte : rle cl du
tissu adipeux ?

T. Measa, , b, c,

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DOI: 10.1016/j.diabet.2009.09.001
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Abstract

For several years now, the epidemiological data have shown an inverse relationship
between birth-weight and the development in later life of cardiovascular disease and
metabolic disorders. The term small for gestational age (SGA) describes a neonate whose
birth-weight is two standard deviations (SD) below the reference mean, corrected for
gestational age and gender. SGA is associated with increased risks of developing
hypertension, insulin resistance and type 2 diabetes. However, the association with an
atherogenic lipid profile is less clear. Nevertheless, all of the components of the metabolic
syndrome are present. Yet, in spite of the large body of data in the literature, the biological
mechanisms underlying this association are still unclear. To explain the association, various
hypotheses have been proposed, pointing to the role of a detrimental fetal environment or
genetic susceptibility, or interaction between the two, and to the particular dynamic changes
in adiposity that occur during catch-up growth. However, not only quantitative, but also
qualitative, abnormalities of adipose tissue have been observed, suggesting a critical role of
this organ in the development of metabolic complications.

Rsum

Une corrlation ngative entre le poids de naissance et la mortalit cardiovasculaire a t

mise en vidence pour la premire fois voici bientt 20 ans. Depuis, de nombreuses tudes
sont venues confirmer ce rsultat. Le petit poids de naissance est dfini comme un poids
et/ou une taille de naissance infrieur(e) deux cart-types, rapport pour lge gestationnel
et selon la distribution de rfrence. Le petit poids de naissance pour lge gestationnel est
aussi li au dveloppement dune HTA, dune obsit, dune insulinorsistance, voire dun
diabte de type 2. Leffet sur le profil lipidique semble plus modeste. Ainsi, les diffrents
composants du syndrome mtabolique sont lis lantcdent de petit poids de naissance.
Plusieurs mcanismes physiopathologiques ont t proposs pour expliquer les liens entre
le petit poids de naissance et le dveloppement, lge adulte, de pathologies
cardiovasculaires et mtaboliques. Le rle de lenvironnement dltre intra-utrin ou celui
des gnes de susceptibilit, voire lassociation des deux, ont t voqus. Le rattrapage
pondral, qui survient dans les premires annes de la vie, semble largement contribuer
ces observations. Le lien avec lindex de masse corporelle (IMC) au moment de
lobservation a t soulign. Le rle de la croissance du tisse adipeux la fois durant la
priode ftale et postnatale semble dterminant pour le dveloppement ultrieur de
troubles mtaboliques chez les sujets qui ont prsent un petit poids de naissance.
Ladaptation de certains organes durant la vie ftale pourraient devenir inapproprie une
fois la priode de restriction passe. Cependant, ces mcanismes restent pour le moment
hypothtiques.

Keywords

SGA;

Low-birth-weight;

Catch-up growth;

Metabolic syndrome;

Adipose tissue;

Review

Mots cls

Petit poids de naissance pour lge gestationnel;

Syndrome mtabolique;

Rattrapage pondral;

Tissu adipeux et composition corporelle;

Revue gnrale

Lifestyle intervention in the management of metabolic syndrome: could we

improve adherence issues?
Evaggelia Fappa, M.Sc.
,
Mary Yannakoulia, Ph.D.
,
Christos Pitsavos, M.D., Ph.D.
,
Ioannis Skoumas, M.D.
,
Stella Valourdou, B.Sc.
,

Christodoulos Stefanadis, M.D., Ph.D.

Received: June 22, 2007; Accepted: November 18, 2007; Published Online:
January 18, 2008
DOI: http://dx.doi.org/10.1016/j.nut.2007.11.008

Abstract

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Abstract

Current guidelines for the treatment of the metabolic syndrome (MetSyn) propose lifestyle
changes (diet and physical activity) as a first-line intervention. However, few studies have
been conducted thus far in this field. Weight loss has been recognized as an important issue
in the management of MetSyn, in addition to exercise training. Moreover, improvement in
MetSyn parameters was sustained only when changes in lifestyle were maintained,
rendering maintenance as an important treatment issue. Multiple follow-up booster sessions
proved more effective in maintaining lifestyle changes than one counseling session at the
end of follow-up. Several behavioral techniques have also been used to improve patients
adherence. Although most of these were found effective in achieving short-term adherence
to the dietary regimen (and exercise treatment), the evidence is limited regarding specific
strategies that are most helpful, in the context of a structured, tailored MetSyn intervention,
for the long-term maintenance of lifestyle changes.
Keywords:
Metabolic syndrome, Obesity, Lifestyle intervention, Diet, Adherence, Behavior
modification
Psychosomatic Medicine:
February/March 2011 - Volume 73 - Issue 2 - pp 158-165
doi: 10.1097/PSY.0b013e3182037315
Original Articles
Psychological Distress Predicts the Development of the Metabolic Syndrome: A
Prospective Population-Based Study

Puustinen, Pekka Johannes MD, MPH; Koponen, Hannu MD, PhD;

Kautiainen, Hannu BA; Mntyselk, Pekka MD, PhD; Vanhala, Mauno MD,
PhD

Abstract

Objective: To examine prospectively the association of psychological distress with the

development of the metabolic syndrome (MetS) and the potential influence of demographic
characteristics, health behaviors, and inflammation in this association.
Methods: A total of 466 (n = 185 males; 281 females) subjects, aged 36 to 56 years, and
free of MetS at baseline, participated in a population-based study from 1997 to 1998 and
again from 2004 to 2005. Mean observation time was 6.4 years. Various clinical,
biochemical, and behavioral factors were measured at baseline, including assessment of
psychological distress using the 12-item General Health Questionnaire. The development of
MetS was measured at follow-up based on National Cholesterol Education Program
criteria.
Results: Subjects with high psychological distress at baseline (General Health
Questionnaire scores, 412) were more than twice as likely to develop MetS than those
with low psychological distress (odds ratio, 2.18; 95% confidence interval, 1.303.64).
Adjustments for 1) age, gender, and sociodemographic variables; 2) health behaviors
(smoking, alcohol use, and leisure time physical activity); and 3) C-reactive protein in the
analysis diminished the odds of developing MetS in the distressed group (odds ratio, 1.87;
95% confidence interval, 1.83 and 1.81, respectively); however, the association remained
statistically significant (p = .025.038).
Conclusions: Psychological distress at baseline increases the risk of developing MetS
during follow-up. This association remained robust after adjusting for age, gender,
sociodemographic variables, baseline health behaviors, and C-reactive protein. These
prospective findings are evidence of a significant association between psychological
distress and the development of MetS.
MetS = metabolic syndrome; GHQ-12 = 12-item General Health Questionnaire; SD =
standard deviation; OR = odds ratio; CI = confidence interval; CRP = C-reactive protein;
hsCRP = high-sensitivity C-reactive protein; HDL = high-density lipoprotein; NCEP-ATP
III = National Cholesterol Education Program-Adult Treatment Panel III; BDI = Beck
Depression Inventory.
Racial/ethnic discrepancies in the metabolic syndrome begin in childhood and
persist after adjustment for environmental factors
S.E. Walker
,

M.J. Gurka
,
M.N. Oliver
,
D.W. Johns
,
M.D. DeBoer
Received: October 7, 2009; Received in revised form: May 13, 2010; Accepted:
May 20, 2010; Published Online: August 13, 2010
DOI: http://dx.doi.org/10.1016/j.numecd.2010.05.006

Abstract

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Abstract
Background and Aims

Evaluation of metabolic syndrome (MetS) characteristics across an age spectrum from

childhood to adulthood has been limited by a lack of consistent MetS criteria for children
and adults and by a lack of adjustment for environmental factors. We used the pediatric and
adult International Diabetes Federation (IDF) criteria to determine whether gender-specific
and race-specific differences in MetS and its components are present in adolescents as in
adults after adjustment for socio-economic status (SES) and lifestyle factors.
Methods and Results

Waist circumference, blood pressure, triglycerides, HDL cholesterol, and fasting glucose
measures were obtained from 3100 adolescent (1219years) and 3419 adult (2069years)
non-Hispanic white, non-Hispanic black, and Mexican-American participants of the 1999
2006 National Health and Nutrition Examination Surveys. We compared odds of having
MetS and its components across racial/ethnic groups by age group, while adjusting for
income, education, physical activity and diet quality. After adjusting for possible
confounding influences of SES and lifestyle, non-Hispanic-black adolescent males

exhibited a lower odds of MetS and multiple components (abdominal obesity,

hypertriglyceridemia, low HDL, hyperglycemia) compared to non-Hispanic-white
and Mexican-American adolescents. Compared to non-Hispanic-white adolescent males,
Mexican-American adolescent males had less hypertension. There were no differences in
MetS prevalence among adolescent females, though non-Hispanic-black girls exhibited less
hypertriglyceridemia.
Conclusion

Racial/ethnicity-specific differences in MetS and its components are present in both

adolescence and adulthood, even after adjusting for environmental factors. These data help
strengthen arguments for developing racial/ethnic-specific MetS criteria to better identify
individuals at risk for future cardiovascular disease.
Keywords:
Metabolic syndrome, Adolescence, Insulin, Race
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Diet, fitness and metabolic syndrome The DRs EXTRA Study
R. Kouki

,
U. Schwab
,
T.A. Lakka
,
M. Hassinen
,
K. Savonen
,
P. Komulainen
,
B. Krachler
,
R. Rauramaa
Received: June 18, 2010; Received in revised form: September 27, 2010;
Accepted: October 11, 2010; Published Online: December 27, 2010
DOI: http://dx.doi.org/10.1016/j.numecd.2010.10.008

Abstract

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Abstract
Background and Aims

To study the independent and combined associations of diet and cardiorespiratory fitness
with the prevalence of the metabolic syndrome (MetS).

Methods and Results

We studied a population-based random sample of 663 men and 671 women 5778 years of
age at baseline of an ongoing randomised controlled trial. Based on a 4-day food record a
diet score was created according to goals achieved (vegetables 400 g/day, fish 2
servings/week, fibre 14 g/1000 kcal, saturated fat <10 E%/day). Cardiorespiratory fitness
was measured as maximal oxygen uptake (VO2 max) in a maximal symptom-limited bicycle
ergometer test. MetS was defined by the National Cholesterol Education Program criteria.
The lowest prevalence of MetS (5%) was observed among individuals in the highest VO2 max
tertile and achieving 34 dietary goals. The highest prevalence (55%) was observed among
those in the lowest VO2 max tertile and achieving none of the dietary goals. Among
individuals in the highest VO2 max tertile, the odds ratio of having MetS was 0.04 (95% CI
0.020.10) for those achieving 34 dietary goals, 0.07 (0.040.14) for those achieving 12
dietary goals, and 0.16 (0.070.37) for those achieving none of the dietary goals compared
with individuals in the lowest VO2 max tertile and achieving none of the goals after
adjustment for confounding factors.
Conclusion

Healthy diet and higher levels of cardiorespiratory fitness are associated with a reduced risk
of having MetS. However, fitness seems to have a stronger association with MetS than diet.
Clinical Trial Registry No.: ISRCTN45977199, September 13 2006.
Keywords:
Diet, Cardiorespiratory fitness, Metabolic syndrome, Ageing
Abbreviations:
Nutritional strategies in the prevention and treatment of metabolic syndrome

Sabrina E. Feldeisen,a Katherine L. Tuckera

a

Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at

Tufts University, 711 Washington Street, Boston, MA 02111, USA.
Corresponding author (email: katherine.tucker@tufts.edu)

Published on the web 29 January 2007.

Received June 30, 2006. Accepted September 7, 2006.

Applied Physiology, Nutrition, and Metabolism, 2007, 32(1): 46-60, 10.1139/h06-101

Abstract

The metabolic syndrome (MetS) is a clustering of metabolic abnormalities that increase the
risk of developing atherosclerotic cardiovascular disease and type 2 diabetes. The exact
etiology remains unclear, but it is known to be a complex interaction between genetic,
metabolic, and environmental factors. Among environmental factors, dietary habits are of
central importance in the prevention and treatment of this condition. However, there is
currently no firm consensus on the most appropriate dietary recommendations. General
recommendations include decreasing obesity, increasing physical activity, and consuming
an anti-atherogenic diet, and have traditionally focused on low total fat intake. A major
problem with the focus on low fat is that high-carbohydrate diets can contribute to
increasing triglyceride and decreasing high-density lipoprotein (HDL) concentrations. Lowcarbohydrate diets have been popular in recent years. However, such diets are typically
higher in saturated fat and lower in fruits, vegetables, and whole grains than national
dietary recommendations. More recently the quality of carbohydrate has been studied in
relation to MetS, including a focus on dietary fiber and glycemic index. Similarly, there has
been a move from limiting total fat to a focus on the quality of the fat, with evidence of
beneficial effects of replacing some carbohydrate with monounsaturated fat. Other nutrients
examined for possible importance include calcium, vitamin D, and magnesium. Together,
the evidence suggests that the components of diet currently recommended as healthy are
likely also protective against MetS, including low saturated and trans fat (rather than low
total fat) and balanced carbohydrate intake rich in dietary fiber, as well as high fruit and
vegetable intake (rather than low total carbohydrate); and the inclusion of low-fat dairy
foods. Accelerating research on genediet interactions is likely to contribute interesting
information that may lead to further individualized dietary guidance in the future.
Keywords: metabolic syndrome, dietary recommendations, waist circumference, blood pressure, dietary
pattern

References

Alberti KG, Zimmet P, Shaw J. 2006. Metabolic syndromea new worldwide definition. A Consensus Statement from the International Diabetes
Federation. Diabet. Med. 23: 469-480 CrossRef, Medline.

Appel LJ, Moore TJ, Obarzanek E, Vollmer WM, Svetkey LP, Sacks FM, et
al.. 1997. A clinical trial of the effects of dietary patterns on blood
pressure. DASH Collaborative

Psychological risk factors and the metabolic syndrome in patients with coronary
heart disease: Findings from the Heart and Soul Study

Beth E. Cohen
,
Praveen Panguluri
,
Beeya Na
,
Mary A. Whooley
Received: September 18, 2008; Received in revised form: February 3, 2009;
Accepted: February 10, 2009;
DOI: http://dx.doi.org/10.1016/j.psychres.2009.02.004

Abstract

Full Text

References

Abstract

Psychological factors, such as depression and anxiety, are independently associated with an
increased risk of both diabetes mellitus and cardiovascular disease, but the reasons for these
associations are unknown. We sought to determine whether psychological factors were
associated with a greater prevalence of the metabolic syndrome in patients with coronary
heart disease, and the extent to which such an association may be explained by
socioeconomic status, health behaviors, and biological mediators. We conducted a crosssectional study of 1024 outpatients with stable coronary heart disease. Psychological
factors, including depressive and anxiety symptoms, hostility, anger, and optimism
pessimism, were assessed using validated standardized questionnaires. The presence or
absence of the metabolic syndrome was determined using the criteria outlined by the
National Cholesterol Education Program, Adult Treatment Panel III. Higher levels of
depression, anger expression, hostility, and pessimism were significantly associated with
increased prevalence of the metabolic syndrome. These associations were explained by
differences in socioeconomic status and health behaviors. Additional adjustment for
potential biological mediators had little impact. Further research is needed to determine
whether addressing socioeconomic and behavioral factors in people with depression or high
levels of anger or hostility could reduce the burden of the metabolic syndrome.