Moderate-Vigorous Physical Activity across Body Mass Index in Females: Moderating Effect of Endocannabinoids and Temperament
ABSTRACT Background: Endocannabinoids and temperament traits have been linked to both physical activity and body mass index (BMI) however no study has explored how these factors interact in females. The aims of this cross-sectional study were to 1) examine differences among distinct BMI groups on daytime physical activity and time spent in moderate-vigorous physical activity (MVPA), temperament traits and plasma endocannabinoid concentrations; and 2) explore the association and interaction between MVPA, temperament, endocannabinoids and BMI.
- SourceAvailable from: William D Johnson[Show abstract] [Hide abstract]
ABSTRACT: The 2005-2006 National Health and Nutrition Examination Survey (NHANES) is used to describe an accelerometer-derived physical activity/inactivity profile in normal weight (BMI < 25 kg/m2), overweight (25 </= BMI < 30 kg/m2), and obese (BMI >/= 30 kg/m2) U.S. adults. We computed physical activity volume indicators (activity counts/day, uncensored and censored steps/day), rate indicators (e.g., steps/minute), time indicators (employing NHANES activity counts/minute cut points to infer time in non-wear, sedentary, low, light, moderate, and vigorous intensities), the number of breaks in sedentary time (occasions when activity counts rose from < 100 activity/counts in one minute to >/= 100 activity counts in the subsequent minute), achievement of public health guidelines, and classification by step-defined physical activity levels. Data were examined for evidence of consistent and significant gradients across BMI-defined categories. In 2005-2006, U.S adults averaged 6,564 +/- SE 107 censored steps/day, and after considering non-wear time, they spent approximately 56.8% of the rest of the waking day in sedentary time, 23.7% in low intensity, 16.7% in light intensity, 2.6% in moderate intensity, and 0.2% in vigorous intensity. Overall, approximately 3.2% of U.S. adults achieved public health guidelines. The normal weight category took 7,190 +/- SE 157 steps/day, and spent 25.7 +/- 0.9 minutes/day in moderate intensity and 7.3 +/- 0.4 minutes/day in vigorous intensity physical activity. The corresponding numbers for the overweight category were 6,879 +/- 140 steps/day, 25.3 +/- 0.9 minutes/day, and 5.3 +/- 0.5 minutes/day and for the obese category 5,784 +/- 124 steps/day, 17.3 +/- 0.7 minutes/day and 3.2 +/- 0.4 minutes/day. Across BMI categories, increasing gradients and significant trends were apparent in males for sedentary time and decreasing gradients and significant trends were evident in time spent in light intensity, moderate intensity, and vigorous intensity. For females, there were only consistent gradients and significant trends apparent for decreasing amounts of time spent in moderate and vigorous intensity. Simple indicators of physical activity volume (i.e., steps/day) and time in light, moderate or vigorous intensity physical activity differ across BMI categories for both sexes, suggesting that these should continue to be targets for surveillance.International Journal of Behavioral Nutrition and Physical Activity 01/2010; 7:60. · 3.68 Impact Factor
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ABSTRACT: To estimate the overall prevalence and absolute burden of overweight and obesity in the world and in various regions in 2005 and to project the global burden in 2030. Pooling analysis. We identified sex- and age-specific prevalence of overweight and obesity in representative population samples from 106 countries, which cover approximately 88% of the world population, using MEDLINE and other computerized databases, supplemented by a manual search of references from retrieved articles. Sex- and age-specific prevalence of overweight and obesity were applied to the 2005 population to estimate the numbers of overweight and obese individuals in each country, each world region and the entire world. In addition, the prevalence, with and without adjusting for secular trends, were applied to the 2030 population projections to forecast the number of overweight and obese individuals in 2030. Overall, 23.2% (95% confidence interval 22.8-23.5%) of the world's adult population in 2005 was overweight (24.0% in men (23.4-24.5%) and 22.4% in women (21.9-22.9%)), and 9.8% (9.6-10.0%) was obese (7.7% in men (7.4-7.9%) and 11.9% in women (11.6-12.2%)). The estimated total numbers of overweight and obese adults in 2005 were 937 million (922-951 million) and 396 million (388-405 million), respectively. By 2030, the respective number of overweight and obese adults was projected to be 1.35 billion and 573 million individuals without adjusting for secular trends. If recent secular trends continue unabated, the absolute numbers were projected to total 2.16 billion overweight and 1.12 billion obese individuals. Overweight and obesity are important clinical and public health burdens worldwide. National programs for the prevention and treatment of overweight, obesity and related comorbidities and mortalities should be a public health priority.International journal of obesity (2005) 08/2008; 32(9):1431-7. · 5.22 Impact Factor
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ABSTRACT: The effects of physical exercise stress on the endocannabinoid system in humans are almost unexplored. In this prospective study, we investigated in a crossover design and under field conditions at different altitudes the effects of physical exercise on the endocannabinoid system (ECS) in 12 trained healthy volunteers. For determination of alterations on the ECS three different protocols were analyzed: Protocol A (physical exercise at lower altitude) involved strenuous hiking below 2,100 m, whereas Protocol B (physical exercise by active ascent to high altitude) involved hiking up to 3,196 m, an accommodation at the cottage and a descent the next day. Protocol C (passive ascent) included a helicopter ascent to 3,196 m, an overnight stay at this altitude and a flight back to the base camp the following day. The cumulative hiked altitude in Protocol A and B was comparable (~1,650 m). The blood EC concentrations of anandamide increased significantly in Protocol A/B from baseline (T0) 0.12 ± 0.01/0.16 ± 0.02 (mean ± SEM) to 0.27 ± 0.02/0.42 ± 0.02 after exercise (T1) (p < 0.05). Anandamide levels in Protocol C remained stable at 0.20 ± 0.02. We conclude that the ECS is activated upon strenuous exercise whereas the combination with hypoxic stress further increases its activity. The reduced partial pressure of oxygen at high altitude alone did not affect this system. In summary, physical exercise activates the endocannabinoid system, whereas the combination with high altitude enhances this activation. This discloses new perspectives to adaptation mechanisms to physical exercise.Arbeitsphysiologie 11/2011; 112(7):2777-81. · 2.30 Impact Factor
Moderate-Vigorous Physical Activity across Body Mass
Index in Females: Moderating Effect of
Endocannabinoids and Temperament
Fernando Ferna ´ndez-Aranda1,2,3*", Sarah Sauchelli1", Antoni Pastor2,4,5, Marcela L. Gonzalez6,
Rafael de la Torre2,5,7, Roser Granero2,8, Susana Jime ´nez-Murcia1,2,3, Rosa Ban ˜os2,9, Cristina Botella2,10,
Jose M. Ferna ´ndez-Real2,11, Jose C. Ferna ´ndez-Garcı ´a2,12, Gema Fru ¨hbeck2,13, Javier Go ´mez-Ambrosi2,13,
Roser Rodrı ´guez2,11, Francisco J. Tinahones2,12, Jon Arcelus14, Ana B. Fagundo1,2, Zaida Agu ¨era1,2,
Jordi Miro ´7, Felipe F. Casanueva2,15*
1Department of Psychiatry, University Hospital of Bellvitge-IDIBELL, Barcelona, Spain, 2CIBER Fisiopatologı ´a Obesidad y Nutricio ´n (CIBERobn), Instituto Salud Carlos III,
Madrid, Spain, 3Department of Clinical Sciences, School of Medicine, University of Barcelona, Barcelona, Spain, 4Department of Pharmacology, School of Medicine,
Universitat Auto `noma de Barcelona, Barcelona, Spain, 5Human Pharmacology and Clinical Neurosciences Research Group, Neuroscience Research Program, IMIM
(Hospital del Mar Medical Research Institute), Barcelona, Spain, 6Department of Psychology, Universitat Rovira i Virgili, Tarragona, Spain, 7Department of Experimental
and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain, 8Departament de Psicobiologia i Metodologia, Universitat Auto `noma de Barcelona, Barcelona, Spain,
9Department of Psychological, Personality, Evaluation and Treatment of the University of Valencia, Valencia, Spain, 10Department of Basic Psychology, Clinic and
Psychobiology of the University Jaume I, Castello ´, Spain, 11Department of Diabetes, Endocrinology and Nutrition, Institut d’Investigacio ´ Biome `dica de Girona (IdlBGi)
Hospital Dr Josep Trueta, Girona, Spain, 12Department of Diabetes, Endocrinology and Nutrition, Hospital Clı ´nico Universitario Virgen de Victoria, Ma ´laga, Spain,
13Department of Endocrinology and Nutrition, Clı ´nica Universidad de Navarra, University of Navarra, Pamplona, Spain, 14Eating Disorders Service, Glenfield University
Hospital, Leicester, United Kingdom, 15Department of Medicine, Endocrinology Division, Santiago de Compostela University, Complejo Hospitalario Universitario,
Santiago de Compostela, Spain
Background: Endocannabinoids and temperament traits have been linked to both physical activity and body mass index
(BMI) however no study has explored how these factors interact in females. The aims of this cross-sectional study were to 1)
examine differences among distinct BMI groups on daytime physical activity and time spent in moderate-vigorous physical
activity (MVPA), temperament traits and plasma endocannabinoid concentrations; and 2) explore the association and
interaction between MVPA, temperament, endocannabinoids and BMI.
Methods: Physical activity was measured with the wrist-worn accelerometer Actiwatch AW7, in a sample of 189 female
participants (43 morbid obese, 30 obese, and 116 healthy-weight controls). The Temperament and Character Inventory-
Revised questionnaire was used to assess personality traits. BMI was calculated by bioelectrical impedance analysis via the
TANITA digital scale. Blood analyses were conducted to measure levels of endocannabinoids and endocannabinoid-related
compounds. Path-analysis was performed to examine the association between predictive variables and MVPA.
Results: Obese groups showed lower MVPA and dysfunctional temperament traits compared to healthy-weight controls.
Plasma concentrations of 2-arachidonoylglyceryl (2-AG) were greater in obese groups. Path-analysis identified a direct effect
between greater MVPA and low BMI (b=20.13, p=.039) and high MVPA levels were associated with elevated anandamide
(AEA) levels (b=0.16, p=.049) and N-oleylethanolamide (OEA) levels (b=0.22, p=.004), as well as high Novelty seeking
(b=0.18, p,.001) and low Harm avoidance (b=20.16, p,.001).
Conclusions: Obese individuals showed a distinct temperament profile and circulating endocannabinoids compared to
controls. Temperament and endocannabinoids may act as moderators of the low MVPA in obesity.
Citation: Ferna ´ndez-Aranda F, Sauchelli S, Pastor A, Gonzalez ML, de la Torre R, et al. (2014) Moderate-Vigorous Physical Activity across Body Mass Index in
Females: Moderating Effect of Endocannabinoids and Temperament. PLoS ONE 9(8): e104534. doi:10.1371/journal.pone.0104534
Editor: Luı ´sa M. Seoane, Complexo Hospitalario Universitario de Santiago, Spain
Received March 7, 2014; Accepted July 10, 2014; Published August 7, 2014
Copyright: ? 2014 Ferna ´ndez-Aranda et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This manuscript was supported by grants from Instituto Salud Carlos III (FIS PI11/210 and CIBERobn) and DIUE de la Generalitat de Catalunya (2009 SGR
718), Spain. CIBERObn is an initiative of ISCIII. Sarah Sauchelli is recipient of a pre-doctoral Grant (2013–17) by IDIBELL. Jose C. Ferna ´ndez-Garcı ´a is recipient of a
‘Rio Hortega’ contract from ‘Instituto de Salud Carlos III’, Madrid, Spain (CM12/00059). The funders had no role in the study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
Competing Interests: Co-author Dr. Susana Jime ´nez-Murcia is currently an Academic Editor for this journal. However this does not alter the authors’ adherence
to PLOS ONE Editorial policies on sharing data and materials and criteria.
* Email: email@example.com (FF-A); firstname.lastname@example.org (FFC)
" FF-A and SS are joint first authors on this work.
PLOS ONE | www.plosone.org1August 2014 | Volume 9 | Issue 8 | e104534
Data Availability: The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the article.
There is a growing prevalence of obesity and overweight
worldwide. A fall in energy expenditure is believed to be one of the
leading lifestyle changes boosting the notable spread of obesity .
Prolonged sedentary behavior has been strongly associated with
this extreme weight condition and a consequent increase in the
likelihood of cardiovascular diseases, hypertension, type 2 diabetes,
and osteoporosis . Differently, regular exercise or structured
moderate-vigorous physical activity (MVPA) facilitates weight
These changes in physical activity (PA) patterns are of particular
concern for females. The prevalence of obesity has been estimated
to be greater among females than males (11.9% versus 7.7%)
across all studied world regions . In addition, females spend less
time engaging in MVPA and more in sedentary activities, a gender
difference especially seen among younger adults . Given this
evidence, and that the decline in PA over time is especially present
among females , there is an urgent need to understand the
mechanisms underlying the inter-individual fluctuations in struc-
tured PA and their relationship to body mass index (BMI) in
Moderate-Vigorous Physical Activity /BMI and
Biological models have been proposed to explain individual
differences in MVPA. Studies have identified the role of the
endocannabinoid (eCB) system in the engagement and mainte-
nance of structured PA, interacting with the reward neurosystem
of exercise [6,7]. It has been suggested that the beneficial effects of
PA for cognitive function may be partly related to the eCB system
. The eCB system is also known for its modulation of cognitive
and emotional behavior  and for its extensive central and
peripheral control of energy balance . The eCBs 2-
arachidonoylglycerol (2-AG) and anandamide (AEA) are the
endogenous lipid mediators of this system and have similar actions
to those of the exogenous plant cannabinoid D9-tetrahydrocanna-
bionol (THC). ECBs stimulate appetite and food intake by
intensifying the orosensory reward of food, which takes place via
the activation of the CB1 receptors of the central nervous system.
It is also believed that the motivation to ingest is modulated by
interactions between the eCB and opioid systems . ECBs may
additionally be involved in the peripheral regulation of feeding
since intestinal levels of AEA have been found to increase under
food deprivation and decrease during re-feeding . The
opposite pattern occurs with N-oleoylethanolamide (OEA), an
eCB-related compound but non-CB1 receptor ligand with
anorectic effects . Upon the ingestion of fat, OEA is formed
in the intestine and activates the intestinal peroxisome proliferator-
activated receptor alpha (PPARa), which sends a satiety signal
through the vagus nerve .
An over-activation of the eCB system has been associated with
obesity and abnormal eating behavior . The eCB system is
also involved in lipid and glucose metabolism and its peripheral
dysregulation in obesity affects several organs that participate in
energy homeostasis including the liver, pancreas, adipose tissue
and skeletal muscle . Studies of the eCB system in human
subjects have reported that in the obese condition plasma levels of
2-AG are increased [17,18], while other studies have also reported
elevated AEA plasma levels in obese subjects compared to lean
In animal and human studies [11,19,20], both N-acylethano-
lamides AEA and OEA, as well as other analogs such as N-
palmitoylethanolamide (PEA), have been found to increase shortly
after intense exercise, while 2-AG seems to remain stable. You
et al  found that the gene expression of fatty acid amide
hydrolase (FAAH), enzyme that degrades the N-acyl-ethanola-
mides, is lower in the abdominal adipose of obese women on a
program combining exercise training and a caloric restriction diet.
Dubreucq et al  reported CB1 knockout mice to display 30–
40% less running behavior, and proposed a functional loop
between the eCB system and MVPA. In support, studies have
found that acute administrations of CB1 receptor antagonists or
knocking down CB1 receptors in brain GABA neurons have a
negative effect on wheel running activity in rats and mice .
Further, Avraham et al.  administered the eCBs-related
compound 2-arachidonylglyceryl-ether (2-AGE, Noladin) in Sabra
mice, detecting that high doses of 2-AGE did not alter food intake,
but resulted in weight loss and increased PA. These findings may
suggest an interaction between eCBs, BMI, MVPA and reward
Moderate-Vigorous Physical Activity/BMI and
Cloninger  proposed a psychobiological model of person-
ality comprising four heritable temperament traits: Novelty
seeking, Harm avoidance, Reward dependence, and Persistence.
Some of Cloninger’s temperament traits have been associated with
MVPA. Authors found a negative correlation between MVPA and
Harm avoidance (characterized by inhibition, anxiety and a
pessimistic attitude) and a positive link to low Novelty seeking
(characterized by introversion, lack of enthusiasm, tolerance to
monotony, low response to novelty and low dynamism and
curiosity) . In a meta-analysis, the personality trait extraver-
sion, conceptually related to Novelty seeking, and conscientious-
ness appeared to have a positive effect on structured PA, while
high scores of neuroticism, opposite to extraversion, to be inversely
associated with MVPA . A relationship between specific
temperament traits and BMI has also been described in the
literature. Several studies have connected Novelty seeking with
obesity, although some observe a positive association , while
others did not find significant differences . Further, greater
Harm avoidance scores were found in obese compared to lean
Endocannabinoids and Temperament
The eCB system plays a modulator role in many cognitive and
emotional processes . Studies have shown a link between the
eCB system and Cloninger’s temperament traits. An inverse
relationship was observed between CB1 receptor availability and
Novelty seeking . Further, AEA has been identified as a
substrate of the cytochrome P450 2D6 , and genotypic
variations of this enzyme have been linked to individual differences
in Harm avoidance, socialization ability, and anxiety .
Navarrete et al  compared the genetic expression of dopamine
(DRD2) and cannabinoid (CB1, CB2) receptors in two mouse
strains, observing that the mouse strain displaying greater motor
behavior also presented more exploratory behavior, impulsivity,
and lower attention capacity, and that these were related to CB2
Aims of the study
The literature demonstrates significant relationships between
the eCB system, Cloninger’s temperament traits and MVPA, all
associated with BMI. However, no study has analyzed these
Physical Activity and BMI: eCBs and Temperament
PLOS ONE | www.plosone.org2August 2014 | Volume 9 | Issue 8 | e104534
factors together to assess the modulating effect of eCB functioning
and temperament traits on MVPA and lifestyle PA, and the links
to BMI in females. Therefore, the aims of the present study were
to: 1) examine differences among distinct BMI groups on lifestyle
PA levels and time spent in MVPA, temperament traits and
plasma eCB concentrations; and 2) explore the association and
interaction between MVPA, temperament, eCBs and BMI. Based
on the literature, we hypothesized that: 1) Higher BMI would be
associated with greater sedentary behavior, altered plasma eCBs
levels and a specific temperament profile; 2) MVPA levels would
be linked to specific temperament traits, in particular Novelty
seeking, and altered eCB concentration, in particular augmented
plasma AEA levels; 3) Both temperament and eCBs would be
implicated in the relationship between MVPA and BMI.
Materials and Methods
All participants gave written informed consent and the Ethics
Committees of all the research institutions involved in the data
collection approved the study: Comite ´ E´tico de Investigacio ´n
Clı ´nica del Hospital Universitari de Bellvitge; Comite ` E`tic
d’Investigacio ´ Clı ´nica del Hospital Universitari de Girona Doctor
Josep Trueta; Comite ´ E´tico de Investigacio ´n Clı ´nica del Consorci
Mar Parc de Salut de Barcelona-Parc de Salut Mar; Subcomisio ´n
de Investigacio ´n Clı ´nica del Hospital Universitario ‘‘Virgen de la
Victoria’’; Comite ´ E´tico de Investigacio ´n Clı ´nica de la Universi-
dad de Navarra; Comite ´ E´tico de Investigacio ´n Clı ´nica de Galicia
& Universidad de Santiago de Campostela; Comissio ´ Deontolo ´-
gica de la Universitat Jaume 1. The study was conducted in
accordance with the Declaration of Helsinki.
The sample comprised 189 female individuals, distributed along
the BMI continuum, and included: 30 obese participants
(BMI=30–39.9, kg/m2), 43 morbid obese (BMI $ 40, kg/m2),
and 116 healthy-weight controls (BMI=18.5–29.9 kg/m2). Par-
ticipants were Spanish speakers, with a mean age of 34 years
(SD=12.3) (distribution of mean age by group was: control 27.6 –
SD=7.9–, obese 44.9 –SD=12.9– and morbid obese 43.5 –
SD=10.2–). Seven centers, all involved in the CIBERobn Spanish
Research Network, participated: the Eating Disorders Unit
(Department of Psychiatry, University Hospital of Bellvitge-
IDIBELL, Barcelona), the Department of Endocrinology at the
University Hospital of Santiago (Santiago de Compostela); the
Department of Diabetes, Endocrinology and Nutrition (Clinic
University Hospital Virgen de Victoria, Malaga); the Department
of Endocrinology and Nutrition (University of Navarra, Pam-
plona); the Diabetes, Endocrinology and Nutrition Department,
Biomedical Research Institute of Girona (IdIBGi-Doctor Josep
Trueta Hospital, Girona); the Hospital del Mar Medical Research
Institute (IMIM, Barcelona) and the Department of Basic
Psychology, Clinic and Psychobiology (University Jaume I,
Castello ´n). The obese participants were patients who had been
consecutively referred to the clinics mentioned above. Recruit-
ment of the controls took place by means of word-of-mouth and
advertisements at the local universities. All controls were from the
same catchment area as the obese patients.
Exclusion criteria were: a) having suffered a lifetime history of
Axis I mental disorders since many are linked to altered PA and
eCB levels and temperament styles, especially depression and
eating disorders, which are highly co-morbid with obesity [35,37];
b) having a history of chronic medical illness or a neurological
condition (e.g. Parkinson’s disease) that may affect motor capacity;
c) use psychoactive medication or drugs that influence PA (e.g.
cocaine, beta blockers or thyroid medication) or plasma endo-
cannabinoid concentrations (e.g. cannabis); d) being under 18, as
adolescence is characterized by psychobiological changes, or over
60 given that age-related medical conditions (e.g. arthritis) affect
physical functioning in daily life. Substance abuse/dependence
(including cannabis) and eating disorder diagnoses were conducted
face-to-face using the Structured Clinical Interview for DSM-IV
Axis I Disorders (SCID-I) . The evaluation of general health or
mental illnesses was based on the General Health Questionnaire-
28 (GHQ-28) . Enrolment into the study was between January
2010 and March 2013.
Temperament and Character Inventory-Revised (TCI-R)
This questionnaire is composed of 240-items scored on a
5-point Likert scale and measures personality derived from three
character and four temperament dimensions. The dimensions
reflecting temperament (Harm Avoidance, Novelty seeking,
Reward Dependence and Persistence) were assessed, which
entailed the analysis of 133 items of the total items in the
questionnaire. Evaluation of the Spanish revised version 
generated an internal consistency (coefficient alpha) of 0.87.
Physical Activity was evaluated with Actiwatch AW7 (Acti-
watch AW7; CamNtech Ltd, Cambridge Neurotechnology, Cam-
bridge, UK), a small (3963269 mm), light-weight (10.5 g)
accelerometer that measures activity. The Actiwatch is worn on
the non-dominant wrist for 6 days (4 week days and 1 weekend),
from 00:00 hr on day 1 to 00:00 hr on day 7. PA data was
calculated in the form of activity counts in a 1-minute epoch length
over 24 hours. The counts represent the peak intensity of the
movement detected by the Actiwatch AW7. Only the data
between 7:00hr and 23:00hr was analyzed; a data reduction
procedure that has been recommended and conducted in previous
studies [42,43]. No detected movement for 10 or more consecutive
epochs (10 minutes) was considered as missing (seen as implausible
counts or as periods in which the participant was sleeping). In
addition, a minimum of 4 days of wear was used as criterion to
accept the case. This is the lower recommended minimum to
accurately estimate daily PA in adults . Upon analysis of the
data, there were no cases of 4 or less days of wear. The Actiwatch
7 software (CamNtech Ltd) was used to extract the data. Two PA
variables were assessed:
Daytime PA Daily.
PA was calculated in the form of mean
counts per minute (counts?min21) over the 6 days.
Time in SLPA and MVPA.
during the day spent in sedentary-light PA (SLPA) and MVPA was
calculated using an algorithm proposed by Heil . Employing
the activity monitor Actical (Mini Mitter Co., Inc., Bend, OR),
another Actiwatch produced by the same manufacturer, which
was placed on the ankle, hip and wrist, Heil  developed
algorithms to predict activity energy expenditure (AEE) in children
and adults. To obtain the cut point for MVPA, the formula:
AEE=0.02013+(1.282E-5) x HAC (elaborated for wrist worn
accelerometers) was used. This yielded a cut point of 848
counts?min21. This value predicts a PA intensity of 3 MET,
which corresponds to a brisk walk. The algorithm to predict AEE
in children has been used in a previous study to identify MVPA
from the wrist-worn Actiwatch AW4 (CamNtech Ltd, Cambridge
Neurotechnology, Cambridge, UK), an earlier version of the
Actiwatch AW7 .
The Actiwatch AW4 has reliability as a measure of PA similar to
other accelerometers . Wrist worn accelerometers have been
used to measure PA in various studies [45,47]. They have also
The average amount of time
Physical Activity and BMI: eCBs and Temperament
PLOS ONE | www.plosone.org3 August 2014 | Volume 9 | Issue 8 | e104534
been found to predict a similar amount of variance in energy
expenditure to the hip-placed accelerometers [48,49].
Body Composition was assessed using the Tanita Multi-
Frequency Body Composition Analyzer MC-180MA (Tanita
Corporation, Tokyo, Japan). The Tanita is a weighting instrument
utilizing bioelectrical impedance analysis for the screening of body
fat and composition. This instrument is repeatedly revised in
relation to the reference standards dual-energy X-ray absorpti-
ometry (DEXA) (http://www.bl-biologica.es/tanita_tbf.htm) and
has been validated against other weighing methods . Height
was calculated using a stadiometer.
Endocannabinoids quantification method.
were collected from participants between 8 and 9 am after at least
12 hours of fasting. The blood was centrifuged at 3500 rpm at 4uC
for 15–20 min. Plasma aliquots were stored at 280uC until
analysis. Plasma concentrations of the eCBs AEA (ng/mL) and 2-
AG (ng/mL) were assessed. In addition, the following acyletha-
nolamides OEA (ng/mL) and PEA (ng/mL) were assessed.
The eCB quantification was done with modifications of a
previously described methodology of eCB analysis in brain tissue
. After adding the following amounts of deuterated analogues
(Cayman Chemical, USA) 0.25 ng AEA-d4, 1 ng PEA-d4 and
OEA-d4, 5 ng 2-AG to a 0.5 mL aliquot of plasma, eCBs were
extracted with a liquid-liquid extraction in tert-butyl-methyl-ether
(Merck, Germany) and the extracts analyzed in a LC/MS-MS
system (Agilent 6410, USA). ECBs were separated in a C8 column
(2.16100 mm61.8 mm particle size, Zorbax, Agilent) by gradient
chromatography of a mobile phase of water and acetonitrile
containing 0.1% formic acid (Merck, Germany). The source
operated on the positive electrospray ionization mode and the
detection was done by the multiple reactions monitoring
mechanism (MRM). The following precursor to product ion
transitions were used: m/z 379R287 for 2-AG, m/z 348R62 for
AEA, m/z 326R62 for OEA, m/z 300R62 for PEA, m/z
384R287 for 2-AG-d5, 352R66 for AEA-d4, m/z 330R66 for
OEA-d4 and m/z 304R66 for PEA-d4. ECB quantification was
done by isotopic dilution of the deuterated analogues response.
Variations in precision and accuracy were,15% for the individual
Experienced psychologists and psychiatrists (all extensively
trained in the use of the instruments) completed the clinical and
physical assessment in two structured face-to-face interviews. In
addition to the first clinical interview, temperament and general
health status information was obtained through self-report
questionnaires. Prior to assessment, basic anthropometrical
features were determined by the TANITA and blood samples
were obtained after overnight fasting. The accelerometers
provided in the first interview were collected after 7 days in a
second face-to-face assessment session.
Statistical analysis was carried out with STATA13 for Windows.
Analysis of variance (ANOVA) was used to compare BMI, PA
level and eCBs between diagnostic subtypes (controls, obese and
morbid obese). Polynomial contrasts into ANOVA were explored
by means of linear and quadratic trends, and post-hoc compar-
isons and Cohens’-d coefficients for the effect size of differences
between groups (moderate effect size was considered for |d|$0.50
and good effect size for |d|$0.80).
Structural equation models (SEM) tested the mediational
pathway between temperament scores, MVPA levels, eCBs and
BMI, adjusted by the covariate participants’ age. The mediational
path was considered as adequate when it met previously described
criteria . Overall goodness-of-fit statistics were assessed with
the x2test, the root mean squared error of approximation
(RMSEA), baseline comparison indexes (Comparative Fit Index
CFI and Tucker-Lewis Index TLI) and residuals size (Standard-
ized Mean Squared Residual SMSR). A fit was considered to be
good if : a non-significant result (p..05) was achieved for the
x2test, the RMSEA was,.08, the CFI-TI coefficients were..90
and SRMR was limited to 0.08. The equation level goodness-of-fit
and the effect sizes were estimated through multiple correlation
(mc) and Bentler-Raykov multiple correlation (mc2) .
Comparison of Physical Activity measures, BMI,
Temperament and Endocannabinoids between groups
Results obtained in ANOVA procedures (Table 1) showed
differences between groups of weight for the MVPA means: a
negative linear trend emerged (the higher the weights the lower the
MVPA mean levels, p=.008) and statistical differences for the
pairwise comparison between morbid obese versus controls (f=
219.2, p=.005) were found. No statistical association emerged
between groups of weight and daytime PA levels. Linear trends
appeared for TCI-R temperament scales: Novelty seeking
(decreasing trend), Harm avoidance (increasing trend) and
Persistence scales (increasing trend), and an additional quadratic
trend for Reward dependence. Statistical differences were found
between obese and controls for Novelty seeking (p=.015), Harm
avoidance (p,.001) and Reward dependence (p=.002), and
between morbid obese and controls for Novelty seeking
(p=.038) and Harm avoidance (p,.001). As shown in Table 2,
the eCB 2-AG was associated with the distinct BMI groups:
positive linear and quadratic trends were obtained for this
biological measure and statistical differences emerged in the
post-hoc comparison between both obese and morbid obese versus
Mediation model of Moderate-Vigorous Physical Activity
level when including temperament and biological
Figure 1 shows the path-diagram and standardized structural
coefficients for the mediational model between temperament
traits, eCBs, MVPA level and BMI. Results were adjusted by the
covariate participants’ age. Variables selected for the model
accomplished Baron-Kenny’s requirements for mediational paths.
No reciprocal association between eCBs and BMI were retained
since no statistical effect of eCBs on BMI emerged, and retaining
these parameters affected the fitting. Both low Novelty seeking and
high Harm avoidance scores were predictive of lower MVPA
levels. The eCBs measures AEA and OEA mediated the
association between MVPA levels and BMI: a) high MVPA levels
were associated with high AEA measures, and elevated AEA
values were related to high BMI, b) high MVPA levels were also
related to high OEA levels, and low levels for this cannabimimetic
were associated with higher BMI. MVPA levels and Harm
avoidance scores also showed direct effects with BMI (high BMI
was predicted by high Harm avoidance and low MVPA levels).
Pathway of Figure 1 achieved goodness-of-fit: x2=8.36 (p=.30),
RMSEA=.036, CFI=.99, TLI=.98 and SRMR=.033. Consid-
ering each equation level, MVPA level achieved low effect size
values (mc=.26 and mc2=.07), while BMI obtained higher ones
(mc=.69 and mc2=.48). The overall R2(coefficient of determi-
nation) was very good (R2=0.47).
Physical Activity and BMI: eCBs and Temperament
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Table 1. BMI, PA, temperament, endocannabinoids and endocannabinoids related compounds among study groups.
ANOVA: p-value, trends and contrasts
OB vs CO
MO vs CO
MO vs OB
| d |
| d |
| d |
Body mass index
TCI-R: Harm avoidance
TCI-R: Reward depend.
w: Adjusted mean difference in ANOVA. LT: linear trend. QT: quadratic trend. | d |: Cohen’s-d.
*Bold: significant contrast (.05 level). Italics: moderate to good effect-size (| d |$0.5).
BMI: Body mass index; MVPA: moderate-vigorous physical activity; PA: physical activity; 2-AG: 2- arachidonoylglycerol; AEA: anandamide; OEA: N-oleylethanolamide; PEA: N-palmitoylethanolamine.
Physical Activity and BMI: eCBs and Temperament
PLOS ONE | www.plosone.org5August 2014 | Volume 9 | Issue 8 | e104534
The aims of the present study were to analyze the differences
between extreme BMI groups on daytime PA, MVPA, temper-
ament and eCBs, and explore whether temperament traits and
eCB concentrations are mediators of MVPA in females.
Physical Activity and BMI
As expected, comparison among weight categories showed that
the morbid obese participants displayed the least MVPA
compared to the healthy-weight participants. Differently, daytime
PA did not vary between groups. These findings are in line with
the existing literature. A recent study assessing the effects of
adherence to MVPA guidelines on BMI and waist circumference
detected an inverse association between meeting the PA guidelines
and baseline BMI and waist circumference. However, later linear
regressions demonstrated that only vigorous PA was significantly
correlated with lower BMI . In addition, the authors observed
that only high adherence to the MVPA guidelines resulted in
decreases in BMI and waist circumference, while stable PA had no
effect. Similarly, in another study, a significant trend across weight
categories in PA among females was only observed for the time
spent in vigorous PA . A hypothesis may be that it is a gradual
decrease in time spent in MVPA, rather than daytime activity per
se that increases the risk and maintains the global prevalence of
obesity. As the present study was a cross-sectional, causality cannot
be determined, but our findings suggest that the relationship is
Temperament and BMI
Regarding temperament, both obese groups (obese and morbid
obese), presented a distinct temperament profile from the controls,
characterized by greater scores in Harm avoidance and Reward
dependence, but lower Novelty seeking. Whereas those studies that
included obese participants with comorbid eating disorders
(namely Binge Eating Disorder) found higher impulsivity scores
, those who excluded this group of obese patients reported
lower impulsivity levels . This may explain the reason why the
high Novelty seeking in obese individuals described in the
literature  was not found in the present study, as individuals
with a history of eating disorders were excluded from it. Similar to
previous studies , the obese individuals in our study presented
a temperament profile characterized by passivity, sensitivity,
nervousness, insecurity, and social dependence.
Endocannabinoid concentrations and BMI
One remarkable finding in our study was the elevated level of
plasma 2-AG concentrations found in the obese groups, which is
keeping with the literature . Di Marzo et al  observed that
a lifestyle modification program for obese patients resulted in a fall
of both 2-AG and AEA concentrations, however only 2-AG was
associated with a decrease in visceral adipose tissue, triacylglycerol
concentrations, and HDL3-cholesterol concentrations, which
suggests that these eCBs may have distinct metabolic roles. The
present study therefore provides further support to the increasing
evidence for the involvement of eCBs in fat metabolism
development. Additional research must be conducted to determine
the role of the eCB system in obesity.
Table 2. Results of the SEM evaluating the pathways between personality, MVPA, eCBs and BMI.
Physical Activity and BMI: eCBs and Temperament
PLOS ONE | www.plosone.org6August 2014 | Volume 9 | Issue 8 | e104534
Temperament traits and endocannabinoid factors as
mediators of Moderate-Vigorous Physical Activity and
As expected, objectively measured MVPA was found to be
inversely associated with BMI. Noteworthy, the majority of studies
assessing the relationship between BMI and PA have employed
subjective measures to assess the latter, namely self-reported
questionnaires and surveys. Self-reported PA has been found to
differ from more direct assessments, which questions the reliability
of self-report measures . The use of an accelerometer in a large
sample in the present study therefore overcomes this methodo-
In relation to the association between MVPA and temperament
traits, an interesting link was found between MVPA and Novelty
seeking and Harm avoidance scores. This is in line with other
studies, whereby aspects of Novelty seeking, namely energetic
attitude and exploratory behavior, have been found to be related
to both motoric activity in animals  and weekly hours spent
exercising in humans . Whereas individuals with high scores in
extraversion (corresponding to high Novelty seeking) have a more
sociable and interactive lifestyle, and are thus more likely to be
active , those with low levels of Novelty seeking tend to be
passive, inhibited, and less dynamic, and are therefore expected to
adopt a more sedentary lifestyle . In contrast, the Harm
avoidance temperament trait is associated with the inhibition of
behaviors due to greater pessimistic worry or avoidance  and
sensitivity to pain expectancy . Individuals scoring higher in
this trait are likely to be averse to engaging in MVPA, especially
high contact and risky sports, as they avoid any activity in which
they may be vulnerable to injury.
Consistent with prior animal  and human  studies, our
results showed that AEA and OEA plasma concentrations but not
2-AG were positively associated with MVPA. Authors have
proposed that this may be due to differences in the biosynthesis
and degradation mechanisms . Whereas AEA and OEA are
N-acylethanolamides (NAEs) synthesized from the hydrolysis of N-
arachidonoyl phosphatidylethanolamine (NAPE) and degraded by
the FAAH, 2-AG is synthesized from other precursors (diacylgly-
cerols) and enzymes (diacylglycerol lipases-a and b) and is
primarily degraded by monoacylglycerol lipase (MAGL) .
Therefore, given that these eCBs have distinct metabolic
pathways, a different interaction with MVPA has been proposed
One discrepancy between our results and those of Heyman et al
, is that we did not find an association between MVPA and
PEA despite that PEA shares the same biosynthetic and
degradation pathways of AEA and OEA. This could be because
the eCB levels in this study were measured at the basal state, while
Heyman et al  measured eCB levels after intense exercise. In
support to our data, regarding the specific relationships between
some NAEs and PA, Gasperi et al  found increased activity of
FAAH in the lymphocytes of physically active subjects at resting
condition. It must be noted that blood eCB levels represent the
spillover from many sources and it is not possible to differentiate
the tissue of origin. For instance, Caraceni et al  found that
blood AEA, PEA and OEA levels were correlated with liver
function, but eCB levels may vary differently in different tissues
such as in the intestine or brain [12,56], or in different depots of
the same tissue such as in subcutaneous or visceral fat . The
skeletal muscle itself is altered in obesity, with increased expression
of CB1 receptors and elevated levels of 2-AG without there being
changes in AEA. It has been suggested that, in contrast to 2-AG,
Figure 1. The moderating role of temperament and endocannabinoids on physical activity levels and body mass index. Continuous
line: significant parameter. Structural Equation Model analysis shows that the temperaments low Novelty seeking and low Harm avoidance were
predictive of low physical activity (MVPA) levels. High MVPA levels were associated with high anandamide (AEA) levels and high AEA levels were
associated with high body mass index (BMI). In addition, high MVPA levels were associated with high N-oleylethanolamine (OEA) levels and low OEA
levels were associated with high BMI. A direct effect was found between high MVPA and low BMI and between high Harm avoidance and high BMI.
Physical Activity and BMI: eCBs and Temperament
PLOS ONE | www.plosone.org7 August 2014 | Volume 9 | Issue 8 | e104534
AEA and possibly OEA may have beneficial effects on glucose
uptake and mitochondrial biogenesis in the muscle through the
activation of other receptors such as peroxisome proliferators
(PPARs) or the transient receptor potential vanilloid receptor 1
(TPRV1). In this regard, it has been proposed that PA could be a
complementary approach for the treatment of obesity without the
side effects of CB1 antagonists . In addition to the PA
peripheral effects, the potentiation of the eCB system after MVPA
also has positive effects on cognitive functions, again linked to AEA
, which could facilitate the implementation of both preventive
and treatment programs for obesity.
Furthermore, in the current study the eCBs AEA and eCB-
related compound OEA seem to act as contrasting mediators in
the relationship between MVPA and BMI. The underlying
mechanism between MVPA and the eCB system activation is
not yet clear. It could be due to the increases in stress and
glucocorticoid hormones (particularly cortisol) that occur with
structured PA and seem to be implicated in the activation of eCB
signaling . Separately, eCBs have been found to be implicated
in the regulation of appetite (as is the case of marijuana) via the
activation of the reward system . When energy homeostasis is
challenged, such as in situations of food deprivation, an increase in
endocannabinoid levels takes place . The process is associated
with a reinforced pleasure obtained from ingestion and from the
rewarding properties of food [11,67], which may lead to
hyperphagia, overconsumption and consequentially weight gain
. Differently, the eCB-related compound OEA is a putative,
peripheral satiety factor and anorexigen mediator, which promotes
satiety and reduces weight gain by stimulating the vagal sensory
nerves that in turn stimulate the brainstem and hypothalamus
. These findings are reflected in the mediation effect of AEA
and OEA on the relationship between MVPA and BMI obtained
in the current study. MVPA has an inverse direct effect on BMI,
which can be attributed to energy expenditure, and a similar
indirect relationship may also exist mediated by OEA. Yet, MVPA
may also be associated with augmented BMI through the orexigen
effect of AEA.
Finally, Novelty seeking and plasma AEA concentrations were
both found to be positively linked to MVPA. Van Laere et al 
evaluated CB1 receptor availability in temperament, finding
greater global cerebral CB1 receptor availability to be inversely
related to Novelty seeking. Novelty seeking may interact with the
eCB system via the engagement in MVPA. Furthermore, the
activation of this system with exercise appears to result in exercise-
induced analgesia and may be responsible for the reported
runner’s high, a transient and intense feeling of happiness, elation,
and energy . Our results support the concept that individuals
who are high in impulsive traits may engage in PA to achieve a
gratifying state, following a positive reinforcement conditioning,
whereas more passive and less energetic individuals, such as those
who present elevated Harm avoidance, present more sedentary
behavior. Reduction in the BMI might be a consequent effect, but
also may act as a maintaining factor of this vicious circle. Further
research is needed to understand the mechanisms of these
associations. For instance OEA is not a CB1 agonist and it is
best known for acting as a fat sensor in the intestine, but in a recent
report it has been suggested that OEA is also involved in the
reward system by stimulating central dopamine activity  and
may participate in the control of reward-related behaviors through
a PPARa receptor-independent mechanism .
The study has a number of limitations that should be
considered. First, the study focused of females. Future studies
should also assess male participants who are likely to present
distinct PA patterns. Second, the accelerometer was placed in the
non-dominant wrist. Though this instrument permits a more
accurate assessment of PA compared to subjective measures, PA
entailing only lower-body movement may not be adequately
captured. Future studies should place accelerometers to both the
wrist and waist, as well as use self-reported questionnaires in order
to obtain a more complete description of the activity patterns of
participants. It must also be noted that in the current study plasma
eCBs levels were assessed in the morning after an overnight fast,
while MVPA was evaluated throughout the day. Although a link
between time spent in MVPA and circulating eCBs was observed,
a more controlled design should be developed in order to
demonstrate the exact cause-effect mechanism. Finally, the cross-
sectional nature of the study does not permit causality to be
determined. Longitudinal studies should be conducted to evaluate
how temperament in adolescence or young adulthood may predict
the interaction between eCBs, temperament, and MVPA later in
life, and to assess how lifestyle changes with increases in the time
spent engaging in MVPA may be related to alterations in the eCB
system and BMI.
Despite its limitations, this study has several important
strengths, including the substantial sample size. Furthermore,
path-analysis is used in this study as a case of structural equation
modeling (SEM) with exploratory aims, with the advantage
(compared to classical regression models) of allowing the inclusion
of multiple relationships among a set of variables, including
mediational associations. The results obtained constitute empirical
evidence for the development of further theories about the role of
MVPA, endocannabinoids and temperament on BMI.
In conclusion, the present study provides further understanding
of the pathophysiological mechanism involved in PA and obesity
by integrating previously described links between the eCB system,
temperament, MVPA, and BMI, to generate a psychobiological
model of the relationship between engagement in MVPA and
BMI. It was shown that decreases in time spent in MVPA, rather
than overall daytime PA, may be underlying the augmentation in
obesity, and this may occur through the interaction with both
psychological and biological factors. Important clinical conclusions
may be drawn to confront the excess obesity among females.
Future therapeutic approaches aiming at preventing obesity by
reducing sedentary behavior and encouraging exercise, should
consider both physiological and behavioral maintaining factors
(e.g. attitude and motivation, behavioral tasks, environmental
factors, locus of control), and temperament traits. It may be
hypothesized that additional psychological interventions focusing
on improving enthusiastic and inquiring attitudes, positive own
reactions in front of novelty and new goals, might have a positive
secondary influence on patients’ attitude towards MVPA.
Conceived and designed the experiments: FFA SS AP RdlT SJM RB CB
JMFR GF FJT ABF ZA FFC. Performed the experiments: FFA SS AP
JCFG JGA RR ABF ZA. Analyzed the data: RG. Contributed reagents/
materials/analysis tools: FFA SS AP RdlT RB CB JMFR GF JGA FJT
FFC. Wrote the paper: FFA SS AP MLG RdlT SJM RB CB JMFR GF
JGA FJT JA ABF ZA JM FFC.
Physical Activity and BMI: eCBs and Temperament
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Physical Activity and BMI: eCBs and Temperament
PLOS ONE | www.plosone.org 10 August 2014 | Volume 9 | Issue 8 | e104534