The physical activity, stress and metabolic syndrome triangle

17 Pages·2010·0.17 MB·English

obesity reviews
doi:10.1111/j.1467-789X.2009.00680.x
Etiology and Pathophysiology
The physical activity, stress and metabolic syndrome
triangle: a guide to unfamiliar territory for the
obesity researcher
obr_680492..507
M. E. Holmes1, P. Ekkekakis2 and J. C. Eisenmann1
1DepartmentofKinesiology,Centerfor Summary
PhysicalActivityandHealth,MichiganState Research aimed at deciphering the aetiology of obesity and the metabolic syn-
University,EastLansing,MI;2Departmentof drome remains focused on two behavioural factors, namely diet and physical
Kinesiology,IowaStateUniversity,Ames,IA, activity,eventhoughepidemiologicresearchsuggeststhatthesetwocornerstones
USA oftreatmentandpreventionaccountforonlyasmall-to-moderateportionofthe
varianceinthesephenotypes.Inrecentyears,thisobservationhaspromptedthe
Received12May2009;revised4September intensifiedinvestigationofthepathogenicpotentialoffactorsthatextendbeyond
2009;accepted11September2009 the traditional concept of energy imbalance and examine the putative causes of
this imbalance. Psychosocial stress has emerged as one such factor, raising the
Addressforcorrespondence:MEHolmes,3 needforresearcherstobeinformedaboutthisexpansiveandcomplexliterature.
IMSportsCircle,DepartmentofKinesiology, The purpose of this review is twofold (i) To introduce obesity researchers to
MichiganStateUniversity,EastLansing,MI fundamentalconceptsandhistoricallyimportanttheoreticaldevelopmentsinthe
48823,USA.E-mail:[email protected] stress field and (ii) To outline the dyadic and triadic interactions between stress,
physical activity and the metabolic syndrome. Although the expansion of the
research focus to multiple, diverse and interacting putative causal agents will
certainlyincreasethecomplexityoftheresearchenterprise,thisstepseemsessen-
tial for the comprehension and effective response to the continuing rise in the
prevalenceofobesityandthemetabolicsyndrome.
Keywords:Cortisol,catecholamines,exercise,emotion.
obesityreviews(2010)11,492–507
thetic adrenomedullary (SAM) axes. This hypothesis
Introduction
draws upon the linkage between the physiology of the
Conventionally, diet and physical activity are considered stress response, specifically elevated cortisol and cat-
the two cornerstones in the prevention and treatment of echolamine levels, and components of the metabolic syn-
obesity, even though epidemiologic research suggests that drome(8).Severalauthorshaveexaminedtheindependent
diet and physical activity leave a considerable amount of relationships between stress and components of the meta-
the variance unexplained. As the prevalence of obesity bolic syndrome for both adults (9) and children (10,11).
andthemetabolicsyndromecontinuetorise(1),research- Thedyadicrelationshipsbetweenphysicalactivityandthe
ersincreasinglyspeculatethatothergenetic,epigeneticand components of the metabolic syndrome; physical activity
environmentalfactorsmayaugmentthetraditionalconcept and stress; and stress and the metabolic syndrome have
ofenergyimbalanceintheaetiologyandpathophysiology been addressed in the literature. However, the triadic
ofobesityandthemetabolicsyndrome(2–7). systemofinteractionsbetweenphysicalactivity,stressand
One hypothesis implicates perturbations in the function components of the metabolic syndrome has received
of the hypothalamic-pituitary-adrenal (HPA) and sympa- limited attention (12,13).
492 ©2009TheAuthors
Journalcompilation©2009InternationalAssociationfortheStudyofObesity.obesityreviews11,492–507
obesity reviews
Exercise,stressandmetabolicsyndrome M.E.Holmesetal. 493
This emerging multifactorial view of obesity and the day stress-research is confronted’ (15). Several substances
metabolic syndrome presents exciting new avenues for suspected to be the ‘first mediator(s)’ were examined and
exploration but also presents challenges for obesity eliminated as candidates (e.g. adrenaline, noradrenaline,
researchers who are now called to become proficient in acetylcholine,histamine).Itwasonlyshortlybeforetheend
new,unfamiliarandcomplexsubjectsandliteratures.The ofhislifethatSelyegaveseriousconsiderationtotheroleof
purpose of this review is to provide an overview of the psychologicalfactors:
literature linking physical activity, psychosocial stress and
Stressors,itshouldbenoted,arenotexclusivelyphysical
the metabolic syndrome. It begins with a section on the
innature.Emotions,e.g.love,hate,joy,anger,challenge,
definition and scope of stress and continues with sections
andfear,aswellasthoughts,alsocallforththechanges
devoted to the dyadic and triadic relationships between
characteristicofthestresssyndrome.Infact,psychologi-
thesevariables.Itisassumedthatmostreadersarealready
calarousalisoneofthemostfrequentactivators(17).
familiarwithbasicinformationonphysicalactivityandthe
metabolicsyndrome. Althoughextensivereferencestopsychologicalfactorsdid
notstartappearinguntilthelatestagesofhislife,itisalso
importanttopointoutthatSelye’sfirstpertinentobserva-
Stress
tioncameratherearly,albeitasanincidentalsidenote:‘even
mereemotionalstress,forinstance,thatcausedbyimmobi-
Definition and scope
lizingananimalonaboard(takinggreatcaretoavoidany
Contemporaryscientificinterestontheimpactofstresson physicalinjury),provedtobeasuitableroutineprocedure
health stems from a half-page publication by Hans Selye fortheproductionofaseverealarmreaction’(18).
(14) in the journal Nature on 4 July 1936, entitled ‘A Thisobservationbecamethestartingpointforcriticsof
syndromeproducedbydiversenocuousagents’.Init,Selye Selye’s concept of stress from the field of psychology.
outlined a so-called ‘general adaptation syndrome’, which Richard Lazarus (19) focused on the fact that the magni-
manifestsitselfwhenanorganismisexposedtodamaging tudeofhumanstressresponsesistypicallynotproportional
stimuli as diverse as cold, injury, transcision of the spinal tothedegreeofobjectivedanger.Thus,herejectedtheidea
cord, excessive exercise or intoxication. The syndrome, ofstressasapassiveresponseandinsteadproposedthatthe
accordingtoSelye’sdescription,progressesinthreestages, keyinthestressprocessisthesubjectiveappraisalofthreat.
including an initial alarm reaction, a stage of resistance, This appraisal is a cognitive inferential process about the
and,ifthedamagecontinues,exhaustionanddeath.Inthe meaning of the stimulus and its implications for the well-
process, there is characteristic enlargement of the adrenal beingandthegoalsoftheindividual,influencedjointlyby
glands, involution of the thymus and lymph nodes, and the individual’s psychological make-up (e.g. knowledge
ulceration of the stomach. Although the term ‘stress’ did andbeliefs)ontheonehandandthesituationontheother.
notappearinthatfirstpublication,Selyeisresponsiblefor Thisconceptgraduallymaturedintooneofthemostinflu-
assigning to it the meaning it now has in the biomedical entialcognitivetheoriesofstressandemotion(19,20).
literature. The exact definition evolved over a period of
decades. For example, ‘we may define stress as the state
Non-specificity or multihormonal patterning?
manifestedbyaspecificsyndromewhichconsistsofallthe
nonspecifically induced changes within a biologic system’ JohnMason(21–24)focusedhiscritiqueofSelye’sviewof
(15)or,later(andmorefamously),‘stressisthenonspecific stress on the notion of a chemical ‘first mediator’ and the
responseofthebodytoanydemandmadeuponit’(16). fundamental tenet of non-specificity. On the nature of the
These definitions illustrate the central importance in first mediator, Mason agreed with Lazarus in assigning a
Selye’s conceptualization of stress of the notion of non- central role to psychological processes. In his words, the
specificity. Selye insisted that there are striking similarities first mediator ‘may simply be the psychological apparatus
in the way that the body responds and adapts to diverse involvedinemotionalorarousalreactionstothreateningor
challenges from within or outside, regardless of the exact unpleasantfactorsinthelifesituationasawhole’(21).On
natureofthesechallenges.Promptedbythenotionofnon- the concept of non-specificity, Mason was a pioneer in
specificity, much of Selye’s work on stress was devoted to broadeningthescopeofinvestigationsbeyondmorphologi-
thesearchfortheso-called‘firstmediator’,anelusivesub- calchangesinorgansandtissuesandbeyondfocusingona
stance that he believed was the single common signal for single hormone or a single endocrine system. Instead, he
the initiation of the stress response to various stimuli. systematically recorded changes across multiple endocrine
Importantly, the first mediator was sought strictly among systemsinresponsetomultiplechallenges,includingthose
the body’s chemicals: ‘The nature of the alarm-signals, ofpsychologicalnature.Hisconclusionwasthat,contrary
whicharesentoutbyvarioustissuesinthebody,isperhaps to Selye’s strong insistence on non-specificity, there was
oneofthemostfundamentalquestionswithwhichpresent- evidence of patterning and specificity: ‘The picture emerg-
©2009TheAuthors
Journalcompilation©2009InternationalAssociationfortheStudyofObesity.obesityreviews11,492–507
obesity reviews
494 Exercise,stressandmetabolicsyndrome M.E.Holmesetal.
ing so far from our study of multihormonal patterns, in Letusbeginwithwhathasbeen,foroveracentury,the
fact,isonesuggestingthatsuchpatternsareorganizedina dominant model for conceptualizing the similarities and
rather specific or selective manner, depending upon the differences that characterize the subjective states that fall
particularstimulusunderstudy,andprobablyinrelationto within the domain of affect, including moods and emo-
the complex interdependencies in hormonal actions at the tions.Thismodel,knownastheaffectcircumplex(30,31),
metaboliclevel’(23). posits that the global affective space can be defined by
two orthogonal and bipolar dimensions; one represents
affective valence (pleasure vs. displeasure) and the other
The stress axes: specificity revisited
representsthedegreeofactivation(lowvs.high).Different
A tremendous amount of information has emerged on the affective states are considered combinations of various
endocrine, immune and central nervous system responses degrees of the basic elements of valence and activation,
to stress and their interdependencies. Two endocrine such that they can be arranged in circular fashion in the
systemscontinuetoberegardedastheprimarycomponents two-dimensional space defined by these dimensions (see
ofthestressresponse.Onesystemextendsfromtheparvo- Fig.1). States that are experientially similar (e.g. happy,
cellulardivisionoftheparaventricularnucleusofthehypo- glad) are close together on this circle, states that are anti-
thalamus,viatheportalcirculation,totheanteriorlobeof thetical(e.g.happy,sad)are180°apart,andstatesthatare
the pituitary gland and, finally, to the zona fasciculata of unrelatedtoeachother(e.g.tense,excited)areseparatedby
theadrenalcortex.Thissystemiscommonlyreferredtoas 90° angles. The dimensions of valence and activation are
thehypothalamic-pituitary-adrenocortical(HPA)axis.The believedtobethefundamentalbuildingblocksofaffective
threenodesinthisaxisproduce,respectively,corticotropin life and emerge with remarkable consistency across dif-
releasing hormone, adrenocorticotropic hormone and ferent types of dimensional analysis (factor or scaling
cortisol.Theothersystemextendsfromvariousbrainstem analyses), different types of stimuli (words, facial expres-
and limbic nuclei (caudal raphe, ventromedial and rostral sionsofemotion)anddifferentcultures(32,33).
ventrolateralmedulla,theventrolateralpontinetegmentum This dimensional conceptualization of affect is remark-
and the hypothalamic paraventricular nucleus) via the ablyconsistentwithanorganizingframeworkthathasbeen
splanchnicsympatheticgangliontothechromaffincellsof proposedforthespecificityofendocrineresponsestostress.
the adrenal medulla. This system is commonly referred to This framework was proposed independently by two
as the SAM axis. Its end products are the catecholamines researchersastheculminationoflongandprolificcareers.
adrenaline and noradrenaline. Additional details on the OnewasMarianneFrankenhaeuser,whoseworkfocusedon
physiological function and regulation of these systems or humanoccupationalhealthpsychology,andtheotherwas
their interactions with other endocrine and immune JamesHenry,whoseworkwithanimalsfocusedonadapta-
systemsarebeyondthescopeofthisreview.Thisinforma- tiontostressandthemechanismsofcardiovasculardisease
tionisreadilyavailableinphysiologytextbooksandrecent (CVD). Their models postulate that the HPA axis and
reviews (e.g. Bohus etal. (25); Charmandari etal. (26); cortisolseemtobesensitivetodifferencesalongtheaffective
Chrousos(27)). valence dimension (pleasure vs. displeasure), whereas the
Here, we focus on the current status of the specificity SAM axis is primarily sensitive to differences along the
debate and, in particular, the relationship between emo- activation dimension. According to Frankenhaeuser (34),
tionalstatesandtheactivationoftheHPAandSAMaxes. ‘epinephrineisageneral(non-specific)indicatorofmental
Theseissues,despitetheirfundamentalimportance,arenot arousal,increasingregardlessofwhethertheaffectisposi-
frequentlyaddressedintheliteratureand,asaresult,itmay tiveornegative’.Incontrast,‘cortisolgenerallyincreasesin
bedifficultforanewcomertothestressfieldtofullygrasp negativeaffectivestatesonly’.Henry’smodelwassumma-
theirimplications. rizedasfollows:‘Onesystem[HPA]respondswithdistress
Supporting Mason’s earlier findings, contemporary and with euphoria in situations associated, respectively,
researchcontinuestoprovideevidencerefutingthenotion with loss of control and with success; the other [SAM],
of non-specificity. It appears that each stressor and, more whichisactivatedbysituationsdemandingeffort,decreases
specifically,eachstressorateachlevelofintensityorsever- itsresponsewhenrelaxationpredominates’(35).Franken-
ity,hasadistinctandreplicable‘signature’inthepatterning haeuser (34,36) further noted that the cortisol response
of not only hormone levels but also the activity of brain shouldbeexpectedtobestrongerwhendispleasureiscom-
regulatorycentres(28,29).Whatisperhapslesswellunder- bined with low activation (as in exhaustion or boredom)
stoodisthe‘signature’ofdifferentpsychosocialstressorsor thanwhendispleasureiscombinedwithhighactivation(as
emotionalstates.Specifically,thequestionofwhetherpar- infearortension).Frankenhaeuserofferedtheexamplesof
ticulartypesofstressfulsituationsoremotionsarelinkedto depressedpatients,prisonersawaitingtrial,orpeoplewho
particular patterns of neuroendocrine responses remains lost jobs for the former and people under pressure to
openforinvestigation. produce in low-control, coercive jobs for the latter. On
©2009TheAuthors
Journalcompilation©2009InternationalAssociationfortheStudyofObesity.obesityreviews11,492–507
obesity reviews
Exercise,stressandmetabolicsyndrome M.E.Holmesetal. 495
Russell's Circumplex Model
Intense
Worked-up
Wired
Hyper
Nervous Lively
Tense Energetic
Afraid Perky
+ ) Scared Peppy
n (
o
ati ASwafdul HGalpapdy
v Crummy Delighted
cti Grouchy Pleased
A
( -) Fatigued Relaxed
Tired Peaceful
Droopy Calm
Sluggish Tranquil
Still
Inactive
Quiet
Silent
( - ) Valence ( + )
Frankenhaeuser's Specificity Model
Adrenaline Cortisol
n ( + ) n ( + ) hcWoigmehab kaiecnrtei vdwa hwteiiotnhn
o o
ati ati
v v
cti cti
A A
( - ) ( - ) Sclootrwmo nbagicneteirvd aw twhioietnhn
( - ) Valence ( + ) ( - ) Valence ( + )
Henry's Specificity Model
SAM Axis HPA Axis
+ ) FMliogshttl,y W Aidthrednraawlinael: MoFsigtlhy tN, Aorpapdrroeancahli:ne + )
n ( n (
o o
ati ati
v v
cti cti
A A
( - ) ( - )
( - ) Valence ( + ) ( - ) Valence ( + )
Figure1 IllustrationofthecompatibilitybetweenthecircumplexmodelofaffectproposedbyRussellandthemodelsofneuroendocrineresponse
specificityproposedbyFrankenhaeuser(basedonresearchwithhumans)andHenry(basedonresearchwithanimals).HPA,hypothalamic-pituitary-
adrenocortical;SAM,sympetheticadrenomedullary.
©2009TheAuthors
Journalcompilation©2009InternationalAssociationfortheStudyofObesity.obesityreviews11,492–507
obesity reviews
496 Exercise,stressandmetabolicsyndrome M.E.Holmesetal.
the other hand, although Frankenhaeuser (36) noted that themostrelevanttothepathologyofinterestandtherefore
‘the pattern of [epinephrine] and [norepinephrine] secre- essentially dictate what aspect of the response one should
tion from the adrenal medulla tends to be rather similar, examine. The traditional approach has been to consider
irrespectiveofthequalityornatureoftheemotionalexpe- onlytheamplitudeofthestressresponse(e.g.theelevation
rience’,Henry(37,38)maintainedthatadrenalineisprima- ofheartrateorhormonelevels).Theassumptionunderly-
rilyassociatedwithfear,whereasnoradrenalineisprimarily ing this approach, referred to as the ‘hyper-reactivity
associatedwithanger.Today,themodelproposedbyFran- model’,isbasedonthebeliefthatitisthemagnitudeofthe
kenhaeuserandHenryiscommonlyusedastheconceptual stress response that is the ‘toxic element’ or the aspect of
basisforinvestigationsfocusingonHPAandSAMresponses the response most closely associated with stress-related
topsychosocialstressors(39). pathologies.Thisassumptionentailsthat,ifonewishesto
Forresearchersinterestedinstudyingthedynamicsofthe investigatetherelationshipbetweenstressandapathologi-
HPA and SAM axes in response to psychosocial stressors, cal condition (such as CVD or the metabolic syndrome),
this conceptual framework has important implications. If oneshouldtrytorelateameasureofthemagnitudeofthe
the primary target of investigation is the HPA response, stress response (e.g. beatsmin-1 of heart rate, mmHg of
the experimental situation should involve negative affect. bloodpressureornmolL-1ofcortisol)withanindexofthe
Typically, this is accomplished with tasks that allow little pathology of interest (e.g. coronary calcification score,
or no chance for the participants to successfully meet the body mass index or waist circumference). A corollary is
givenperformancegoalandcombinesuchelementsassocial that the effectiveness of interventions designed to reduce
evaluation, loss of control and a sense of helplessness thetoxicsequellaofstress(e.g.exerciseorrelaxationtech-
(40,41).Furthermore,giventherelativelyslowresponseof niques)shouldbejudgedbywhethertheycanattenuatethe
theHPAaxis,thesetasksarealsofairlylongandprotracted. magnitudeofthestressresponse.
Astandardprotocolcommonlyusedfortheinvestigation If one considers the totality of the stress response, it is
oftheHPAresponseistheTrierSocialStressTest(42).This apparentthattheamplitudeoftheresponseisonlyoneway
protocol involves standing in front of a microphone, a to define it and, in many cases, it might not be the most
three-memberpanel,avideocameraandataperecorderand meaningful descriptor. The impact on the body could be
deliveringa5-minspeechasajobapplicant.Afteraprepa- determinedbyseveralothercriteria.Dys-regulationcomes
rationperiod,thespeechisdeliveredbut,uponfinishing,the in many forms. McEwen (48) has used the concept of
participant is told ‘You still have some time left. Please allostaticload,thewearandtearofthebodythatoccursas
continue!’Afterthis,participantsareinstructedtosubtract a result of repeated cycles of adapting to internal and
the number 13 from 1022 as quickly and accurately as external demands, to illustrate what these other forms
possible, only to be told to restart with each mistake. In might be. According to McEwen, the normal course of
differentsamples,thisprotocolhasbeenfoundtoinducea eventsintheprocessof‘allostasis’(i.e.adaptingtochang-
twofoldtofourfoldincreaseinsalivarycortisollevels. ing demands) consists of an appropriately sized stress
Ontheotherhand,iftheprimarytargetofinvestigation responseoftheSAMandHPAaxestohelpusdealwiththe
is the SAM response, the experimental situation should demand,immediatelyfollowedbyarapiddeactivationand
mainlyinvolvehighlevelsofactivationandeffort(ideally, return to baseline. This is what ‘normally happens when
uncontaminatedbyphysicaleffort).Suchtasksshouldbeas the danger is past, the infection is contained, the living
engaging and engrossing as possible, challenging but also environment is improved, or the speech has been given’
offering a reasonable chance of success (so that they do (48).However,thereareatleastfourotherscenarios,each
not elicit a consistently positive or a consistently negative of which can exacerbate the allostatic load. These include
outcome) (43). For additional methodological and techni- (i) Repeated activations with excessive frequency; (ii)
cal considerations (e.g. diurnal patterns, timing of assess- Failure to habituate (i.e. show a gradually attenuating
mentprotocols,analysistechniques),readersarereferredto response to a familiar stressor); (iii) Delayed and slow
otherrecenttutorials(44–47). recoveryandreturntobaselineand(iv)Failureofasystem
torespond,resultingincompensatoryorunregulatedacti-
vationofothersystems(foranapplicationoftheallostatic
Linking psychosocial stress
perspective to the pathophysiology of the metabolic syn-
to pathophysiology
drome, see van Dijk and Buwalda) (49). Chrousos and
Gold(50)havefocusedonthe‘chronicity’and‘excessive-
Identifying the toxic element
ness’ofthestressresponseasitsmostpathogenicelements,
Anotherimportantissuepertainstomodelslinkingpsycho- essentiallyrelayingasimilarmessage:
logical stress to pathophysiology. Such models are impor-
tantfortheappliedresearcherbecausetheycanidentifythe Generally,thestressresponseismeanttobeacuteorat
aspect of the psychobiological response that is potentially least of a limited duration. The time-limited nature of
©2009TheAuthors
Journalcompilation©2009InternationalAssociationfortheStudyofObesity.obesityreviews11,492–507
obesity reviews
Exercise,stressandmetabolicsyndrome M.E.Holmesetal. 497
this process renders its accompanying anti-anabolic, sensitive lipase activity, the chief enzymes involved in the
catabolic, and immunosuppressive effects temporarily conversion of triglycerides to free fatty acids in the circu-
beneficial and of no adverse consequences. Chronicity lation and intracellularly respectively. LPL is responsible
and excessiveness of stress system activation, on the forincreasingtheamountoftriglyceridesattheadipocyte
otherhand,wouldleadtothesyndromalstatethatSelye (70)and,asinsulinresistanceoftenmanifestsconcurrently
describedin1936(50). with visceral adiposity, the increased circulating insulin
exerts anti-lipolytic effects and subsequent decreased
Inotherwords,besideshowlargeastressresponseis,it
lipidmobilization(70).Likewise,cortisolappearstohavea
isalsoimportanttoconsider(i)Howfrequentlyitoccurs;
stimulatory effect on LPL activity when insulin is present
(ii) How long it lasts once it occurs and (iii) How quickly
(71). It is thought that chronic hypersecretion of cortisol
the body returns to baseline (also see the emerging litera-
may lead to impaired feedback and resistance, which
tureonthe‘perseverativecognition’hypothesis)(51–53).
mimicsinsulinresistance.Hormone-sensitivelipaseimparts
One issue of paramount importance not mentioned so
itsmostdeleteriouseffectinthedevelopmentofatheroscle-
farbutanticipatedbythepreviousdiscussiononthe(non-)
roticplaque.Atherogenesisinvolvestheuptakeoflipopro-
specificity of the stress response pertains to the patterning
teins by macrophages, which in turn leads to cellular
oftheresponse(54).Givenwhatisknownabouttheeffects
accumulationofcholesterolandformationoffoamcellsor
of catecholamines and cortisol on metabolic processes,
fatty streaks (72). This process may be exacerbated in
would a SAM-dominant or an HPA-dominant response
personswithadys-regulatedorhyperactivestressresponse
entailequalrisk?Thisisunlikely.Forresearchersinterested
given that glucocorticoids stimulate the esterification of
inobesityandthemetabolicsyndrome,itshouldbenoted
sterolsinsmoothmuscle(73).
that the HPA axis appears to be involved in food intake
Complementarytothedys-regulationoftheHPAaxis,the
and fat deposition more directly and in more ways than
SAMaxisalsoplaysaroleinthepathogenesisofmetabolic
the SAM axis (55–58) and is receiving closer attention
syndrome, particularly with regard to visceral obesity.
in applied research linking endocrine function to energy
Obeseindividualswithadys-regulatedHPAaxisalsohave
balance and metabolism (59). Researchers are urged to
increasedSAMactivity,suggestingthatstresssevereenough
considernotonlythemagnitudeofthestressresponsebut
topromotevisceralobesitymayintensifySAMactivity(74).
also other aspects that may have pathogenic potential,
Additionally, visceral obesity is associated with a greater
includingthenumberorfrequencyofresponsesperday,the
basal SAM activity compared with peripheral obesity or
ability to habituate to familiar stressors, the duration of
subcutaneous abdominal obesity (63). The presence of
stressful episodes, the rate of return to baseline and the
hypertensionwithinthemetabolicsyndromesymptomatol-
patterning of neuroendocrine responses (also see Linden
ogy seems to further intensify sympathetic reactivity. In
etal.(60);Schwartzetal.(61)).
persons with metabolic syndrome whose classification
includedhypertension,SAMactivitywasfoundtobegreater
than in non-hypertensives (75). This could in part be as a
Stress, obesity and the metabolic syndrome:
resultofthedecreasedbaroreflexsensitivitythatisassoci-
possible mechanisms
ated with visceral obesity (76). Because the HPA axis and
Hypercortisolaemia has frequently been associated with locuscoeruleusappeartobeperturbedinobesityandinsulin
adiposity, particularly visceral adiposity (62–64). Visceral resistance (77–81), it has been hypothesized that these
fat accumulation can be viewed as a pathological adapta- attributesofthemetabolicsyndromearedrivenbyexacer-
tion to stress (65) as it is particularly sensitive to cortisol, bated stress reactivity (82) and possibly mediate a causal
perhaps because of the high density and apparent sen- relationshipbetweenpsychosocialvariablesandCVD(83).
sitivity of glucocorticoid receptors in this region. 11b- Evidencelinkingdys-regulationsinboththeHPAandthe
hydroxysteroid dehydrogenase type 1 (11HSD1) has SAMaxestoobesityandthemetabolicsyndromeisaccu-
emerged as a potential vector in the aetiological relation- mulating(84–88).Perhapsthemoststrikingfeatureofthis
ship between stress and obesity (66,67). 11HSD1 appears emerging literature is the diversity of the ways in which
central in the conversion of the inactive cortisone to the ‘stress’hasbeenoperationalized.Thisreflectsthecontinu-
activecortisol(68)andispredominantlyexpressedinmeta- ingabsenceofaguidingoverarchingtheoreticalframework
bolically highly active tissues, including the liver, adipose andamultiplicityofperspectivesabouttheaspectofstress
tissue,lungandareasofthecentralnervoussystem(69).In that carries the greatest pathogenic potential and should
obesity, 11HSD1 activity appears to be magnified at adi- thereforebethefocalvariable.Thus,somestudiesfocuson
pocytesanddepressedattheliver(66),whichcancreatea acute reactivity (with cardiovascular autonomic measures,
stateofhypercortisolaemiaintheviscera. catecholamines or cortisol being used as stress indices),
Hypercortisolaemia also creates favourable conditions somestudiesfocusonchroniclifestress,andsomefocuson
for increased lipoprotein lipase (LPL) and hormone- baseline levels and diurnal patterns (mainly of cortisol).
©2009TheAuthors
Journalcompilation©2009InternationalAssociationfortheStudyofObesity.obesityreviews11,492–507
obesity reviews
498 Exercise,stressandmetabolicsyndrome M.E.Holmesetal.
Excellent reviews have been published on the relationship rence (131). Even after excluding participants who were
betweenstressandgeneralhealth(89–91).Inthefollowing obeseatbaseline(assumingthatobesityisaproxyindicator
sections, we examine studies linking stress reactivity and formetabolicsyndrome),theassociationbetweenexposure
chronicstresstoobesityandthemetabolicsyndrome. toworkstressandmetabolicsyndromeremained(131).
Other prospective cohort studies (Table2) have shown
similar results among diverse populations (132–139).
Acute stress
Moreover,stress-relatedvariableshavelongbeensuspected
Stress reactivity studies have examined the relationship to increase the risk of CVD (132) and all-cause mortality
between the stress response (its amplitude and duration) (132,133). Although establishing a causal relationship
and the risk factors of the metabolic syndrome. The most remainsanongoingchallenge,theevidencelinkingchronic
convincingevidenceemergeswhenexaminingcardiovascu- exposuretostresswithpoormetabolichealthisgrowing.
larandendocrinereactivityinconjunctionwithabdominal
obesity(Table1).Inlaboratorystress-inductionparadigms,
Physical activity, exercise and stress
adiposityisconsistentlyassociatedwithexaggeratedheart
rateandbloodpressureresponses(92–95),possiblydriven Therationaleforemployingphysicalactivityasaninterven-
byincreasedcardiacoutputandtotalperipheralresistance tiontobuffertheharmfuleffectsofstressisbasedonthefact
(96,97). Exaggerated catecholamine (94) and glucocorti- thataboutofexercise(structuredandpurposefulphysical
coid (98–102) responses have also been found to be activity)itselfcanbeastressorand,assuch,itcanengage
associatedwithcentraladiposity.Furthermore,abdominal mostofthesamebiologicalpathwaysaspsychosocialstress
adiposityappearsrelatedtoslowercardiovascular(97,103) (i.e. SAM, HPA, cardiovascular system). Sothmann etal.
and endocrine (99) recovery. As noted earlier, slow recov- (140)conductedanextensivereviewinthemid-1990sand
ery following exposure to stress may suggest increased concludedthataboutofexercisethatisdesignedtoelicitan
allostaticloadorburnout(103,104)andmayincreaserisk improvement in aerobic fitness typically elicits a stress
independentlyofthemagnitudeofthestressresponse. response as well. Thus, the working assumption is that
exercise can produce beneficial adaptations in the stress
pathwayswhileavoidingharmfuleffectsonhealth.Inturn,
Chronic stress
these exercise-induced adaptations are expected to also
Chronic psychosocial stress and associated long-term dys- manifest themselves as responses to psychosocial stressors
regulationofneuroendocrinestressresponseswereinitially thataremodifiedinawaythatentailsreducedpotentialfor
investigatedbyexaminingtherelationshipofthesocioeco- harm. This rationale is referred to in the literature as the
nomic gradient with all-cause and CVD mortality (105– ‘cross-stressoradaptationhypothesis’(140,141).
109). Recent investigations have further examined this Until now, the majority of studies investigating this
relationship along with the influence of persistently nega- hypothesis have utilized measures of cardiorespiratory
tiveemotions.Thelinksbetweenchronicstressandobesity responses (e.g. heart rate, blood pressure) and laboratory
orthemetabolicsyndromeseemparticularlyevidentinthe stressors (e.g. mental arithmetic, Stroop word-colour con-
contextofoccupationalstress(110–114). flict task, hand or foot cold pressor task). Most of these
TheWhitehallIIstudy,afollow-upoftheinitialWhitehall studies are also cross-sectional rather than experimental.
study of the 1960s that linked differences along the social Their results have been summarized in a series of recent
gradientwithmorbidityandmortality,hasbeencrucialin meta-analyses, but the conclusions are not entirely consis-
elucidatingtherelationshipbetweenoccupationalstressand tent(142–144)(Table3).
CVD(115).TheWhitehallIIincludedbaselineassessments Narrative reviews that have focused on neuroendcrine
of cardiovascular health and psychological well-being on responses to stress (SAM, HPA) do not report positive
10308 non-industrial civil servants from 20 departments findings. Péronnet and Szabo concluded: ‘Following an
in central London. Clinical screenings and questionnaire extensivereviewoftheliterature,weareunabletoconfirm
assessments have been conducted every five years. Addi- that physical exercise training results in modification of
tional questionnaire data have been collected in-between sympathetic response to psychosocial stress’ (145). Like-
clinical screenings. There have since been seven follow-up wise,inarecentupdateonthestatusofthecross-stressor
periods, with the final assessment including 67% of the adaptation hypothesis, Sothmann remarked: ‘The few
originalcohort(116).Themainfindingsfromthisstudyare studiesconductedtodatewithhumanssuggestthat,while
shown in Table2 and demonstrate a relationship between exercisetrainingforthreetofourmonthsmayincreasekey
high job strain and effort–reward imbalance and health physiological measures of fitness, it generally has not
(117–130). Additionally, a recent follow-up demonstrated induced changes in stress reactivity as indicated by neu-
a dose–response association between exposure to work- roendocrine measures where a short-term psychosocial
related stress and the odds of metabolic syndrome occur- challenge is the precipitating factor’ (141). Sothmann
©2009TheAuthors
Journalcompilation©2009InternationalAssociationfortheStudyofObesity.obesityreviews11,492–507
obesity reviews
Exercise,stressandmetabolicsyndrome M.E.Holmesetal. 499
ummaryoffindings Aftercontrollingforoverall(BMI)andperipheral(tricepsskin-fold)adiposity,thehighestWHRtertileshowedgreater(i)SBPreactivitytoposturalchangeandvideogameand(ii)DBPreactivitytoposturalchangeandforeheadcoldthanlowesttertile CentralobesityassociatedwithgreaterincreasesinSBPandDBPPeripheralobesityrelatedtogreaterQinresponsetobehaviouralstressor WomenwithhighWHRfoundlaboratorychallengesmorethreateningLeanwomenwithhighWHRlackedhabituationtostressorandcontinuedtosecretemorecortisolonsubsequentdayswhencomparedwithleanwomenwithlowWHRCentralfatisrelatedtogreaterpsychologicalstressandcortisolreactivity CortisolAUCandpeakcortisolreactivityassociatedwithWHRinBED(stressed)group GreaterWCassociatedwithgreaterSBPandDBPreactivityinboysonly IncreasedWHRisassociatedwithlowerQandgreaterTPR,irrespectiveofBMIRelationshipbetweencentraladiposityandcardiovascularreactivitywasonlypartiallyattributabletometabolicsyndrome-relatedfactorsandremainedsignificantaftercontrollingforthem MenwithhigherWHRhadhigherdiurnalACTHbutsimilarcortisolElevatedpulsepressureandheartrateatbaselineandpost-stressorIncreasedurinaryexcretionofcatecholaminemetabolites Significantpositivecorrelationsbetweenserumcortisolduringstressandabdominalsagittaldiameter
S (cid:129) (cid:129) (cid:129) (cid:129) (cid:129) (cid:129) (cid:129) (cid:129) (cid:129) (cid:129) (cid:129) (cid:129) (cid:129) (cid:129)
Stressor(s) Posturalchange,5-minvideogame,foreheadcold Speechtask,coldpressortask Mentalarithmetic,visuospatialpuzzle,speechtask Coldpressortask Mentalarithmetic,mirrorimagetracing,typeAadolescentstructuredinterview,coldpressortask Timedmentalarithmetic Simulationwithcorticotrophin-releasinghormone,arithmeticstresstest Colour-wordtest,backwardsubtraction,coldpressor
Design Experimental Experimental Experimental Experimental Experimental Experimental Experimental Correlational
recoveryandobesity Subjects 95normotensiveadolescents(meanage14.8years)withfamilyhistoryofhypertension 24women(11centralobese,13peripheralobese) 59women,premenopausal 22obesewomen(11BED,11non-BED) 211boysandgirls,14–16years(50%female,50%Black) 29normotensive,apparentlyhealthymen18–22years 50men,45–60years(diabetes-free,BMI25–33) 87obesewomenundertheageof45years(meanage41years)
d
n
a
y
ofstudiesexaminingstressreactivit Focus RelationbetweenWHRandhaemodynamicfunction Relationshipbetweenbodyfatdistributionandhaemodynamicstress WhetherwomenwithhighWHRacrossBMIsconsistentlyshowheightenedcortisolreactivity WHRandcortisolresponsivityinobesewomenwithBED AssociationbetweenWCandcardiovascularstressreactivity Effectsofdegreeofobesityanddistributionofbodyfatoncentralandperipheralhaemodynamics DifferencesbetweengenerallyandabdominallyobesemeninactivityandregulationofHPAandSNS Relationbetweencortisolresponseandbodyfatdistribution
y
ar
m
m
SuTable1 References Barnesetal.(95) Davisetal.(92) Epeletal.(98) Glucketal.(99) Goldbacheretal.(64) Jernetal.(96) Ljungetal.(94) Mårinetal.(100)
©2009TheAuthors
Journalcompilation©2009InternationalAssociationfortheStudyofObesity.obesityreviews11,492–507
obesity reviews
500 Exercise,stressandmetabolicsyndrome M.E.Holmesetal.
ummaryoffindings Bodyfatwassignificantlycorrelatedwithcortisolreactivityinbothstudies(r0.33,r0.52)== WomenwithhighWHRhadhighercortisolattheendofthe60-minstressperiodandlargerAUC Significantpositivecorrelationbetweenstress-relatedcortisolandrecumbentsagittaltrunkdiameter,fastinginsulinandglucose,totalcholesterol,LDLcholesterol,DBP LowerSESassociatedwithdelayedcardiovascularrecovery(bloodpressureandheartrate)aftermentalstress StresstaskselicitedincreasedbloodpressurebecauseofincreasedcardiacactivationandincreasedperipheralresistanceBMIandWHRcross-sectionallyassociatedwithpost-stressrecoveryofSBP,DBPandastandardizedQ Positiveassociationbetweencentraladiposityandstress-inducedbloodpressureandheartratereactivity hypothalamic-pituitary-adrenal;LDL,low-densitye;WC,waistcircumference;WHR,waist-to-hip
S (cid:129) (cid:129) (cid:129) (cid:129) (cid:129) (cid:129) (cid:129) A,nc
Pa
Stressor(s) Study1:first-timetandemskydive;Study2:cognitivetests Anagrams,puzzles,arithmetic,shortspeech Naturallyoccurringstressduringtheday,assessedbythequestion‘Didyoufeelanystressduringthishour?’ Colour-wordinterferencetask,mirrortracing Colour-wordinterferencetaskandmirrortracing Stroopcolour-wordtest,speechtask,mentalarithmetic disease;DBP,diastolicbloodpressure;Hervoussystem;TPR,totalperipheralresist
culareticn
Design Correlational Experimental Observational,correlational Experimentalwithprospectivefollow-up Experimentalwithprospectivefollow-up Experimental massindex;CVD,cardiovasnomicstatus;SNS,sympath
Subjects Study1:56men,22women,18–50years;Study2:14men,6women,18–48years 41women,18–40years 284men,all51yearsofage WhitehallIIcohort(subsetof123menand105women,47–58years) 225menandwomen,47–59years 22olderBlack(11men,11postmenopausalwomen) BED,binge-eatingdisorder;BMI,bodydiastolicbloodpressure;SES,socioeco
ContinuedTable1 ReferencesFocus Mujica-ParodiRelationbetweenbodyfatandcortisoletal.(101)responsetoreal-lifestress Moyeretal.RelationbetweenWHRandcortisol(102)responsetolaboratorystressors RosmondRelationbetweenstress-relatedcortisoletal.(62)(assessed7timesduringrandomday)andbodyfatanddistribution Steptoeetal.Psychobiologicalpathwaysmediating(103)relationshipbetweensocialinequalitiesandCVDrisk SteptoeandRelationshipbetweenadiposityandWardle(97)cardiovascularstressreactivityandrecovery WaldsteinWCinrelationtomentalstress-inducedetal.(93)bloodpressureandheartrateresponseinolderBlackmenandwomen ACTH,adrenocorticotropichormone;AUC,areaunderthecurve;lipoprotein;Q,cardiacoutput;SBP,systolicbloodpressure;DBP,ratio.
©2009TheAuthors
Journalcompilation©2009InternationalAssociationfortheStudyofObesity.obesityreviews11,492–507
obesity reviews
Exercise,stressandmetabolicsyndrome M.E.Holmesetal. 501
Table2 Prospectivecohortstudiesexaminingrelationshipbetweenstressandhealth
Study Subjects Stressmeasures Summaryoffindings
WhitehallII Britishcivilservants(menand Work-relatedstressat (cid:129) Effort–rewardimbalanceatworkisassociatedwith
(107,117–131) women),35–55years, baselineandregular CVDandpooroverallhealth
workingincentralLondonin follow-ups (cid:129) Dose–responseassociationbetweenexposureto
1985–1988 work-relatedstressandtheoddsgeneraland
abdominalobesity
(cid:129) Dose–responseassociationbetweenexposureto
work-relatedstressandtheoddsofmetabolic
syndromeoccurrence
(cid:129) Effectofjobstrainonweightgainorlossis
dependentonbaselineBMI
ThePittCountyStudy Representativesampleof PerceivedStressScale (cid:129) Higherperceivedstressatbaselinepredicteda
(134) BlackpeopleineasternNorth assessedatbaseline greaterchangeinBMIoverthe13-yearfollow-upin
Carolina,aged25–59yearsat womenbutnotinmen
baseline(1988)
HealthandBehaviour Britishyouth(2346boysand PerceivedStressScale (cid:129) WaistcircumferenceandBMIweregreaterin
inTeenagersStudy 1719girls)attendingschool assessedatbaselineand moderate-andhigh-stressgroupscomparedwith
(HABITS)(135) incentralLondon,11–12 annuallyfor5years low-stress,acrossall5years
yearsatbaseline(1999) (cid:129) Perceivedstressdidnotpredictincreasesinwaist
circumferenceorBMIatanytimepoint
FinnishPublicSector Finnishmenandwomenwho Work-relatedstresscontrolvs. (cid:129) Highjobdemandandlowjobcontrolaswellas
CohortStudy(136) participatedintheFinnish demandandeffortvs.reward effort–rewardimbalanceareassociatedwithagreater
PublicSectorCohortStudy assessedatbaseline BMI
HealthyWomenStudy 541healthypremenopausal Self-reportmeasuresof (cid:129) Depression,stressfullifeevents,perceivedstress,
(137) womenwhowerescreened depression,tension,anxiety, angerandtensionwereassociatedwiththe
annuallyforanaverageof15 angerandperceivedstress cumulativeprevalenceofthemetabolicsyndrome,
years evenaftercontrollingforage,education,hormone
replacementandbehaviouralriskfactors
(cid:129) 1SDincreaseindepressionwasassociatedwith
1.21–1.43-foldincreaseinriskofthemetabolic
syndromeduringfollow-up
(cid:129) Onestressfullifeeventoverthepast6monthswas
associatedwith1.49–2.12-foldincreaseinrisk
BrainResource 696adults(51%women), Self-reportofchildhood (cid:129) Thenumberofearlylifestressors(butnotdepression,
InternationalDatabase 18–82years,withouthistory abuseandtrauma;subclinical anxietyorstress)wassignificantlybutweakly
(138) ofneurological,medicalor depression,anxiety,stress associatedwithBMI(r=0.08)
psychiatricdisorders (cid:129) Overweight(17%)andobese(30%)menweremore
likelytoreportahistoryofbeingbulliedorsocially
rejectedcomparedwithnormalweight(9%)
(cid:129) Obesemen(17%)weremorelikelytoreporthistoryof
emotionalabusethanoverweight(6%)andnormal
weight(2%)
(cid:129) Nosignificantdifferencesforwomen
MidlifeintheUnited 633men,722women,25–74 Self-reportedstressrelatedto (cid:129) IncreasedBMIduringfollow-upwasrelatedwith
StatesStudy(139) years,whowerefollowedup work,personalrelationships, financialstress(bothmenandwomen),work-related
foranaverageof9.2years lifeconstraints,finances stressformen,job-relateddemands,perceived
constraintsinlife,straininrelationshipswithfamilyfor
women
BMI,bodymassindex;CVD,cardiovasculardisease;SES,socioeconomicstatus.
added that ‘it is theoretically reasonable to postulate studiesthathavebeenconducted(whichissubstantial)but
that...a beneficial effect should be present, but the rather the result of the low methodological quality (with
experimentalapproachestodatehaveofferedlimitedcon- only a few of the studies being prospective randomized
firmingdatainthehuman’(141). experimentaltrials)andconceptualsophistication.
Clearly, this line of research is still at an early stage. A striking feature of the meta-analyses summarized in
However, this is not really a function of the number of Table3 is not the magnitude of the effects but rather the
©2009TheAuthors
Journalcompilation©2009InternationalAssociationfortheStudyofObesity.obesityreviews11,492–507