Interventions against obesity through increased lipolysis in adipose tissue

Obesity is a disease of excess adiposity affecting> 17% of men and >20% of women in Britain. Clinically, it is defined by a Body Mass Index (BMI, kg/m2) of 2:30. Obesity is a confounding factor that promotes insulin resistance, hyperinsulinaemia and type 2 diabetes. Type 2 diabetes accounts for >90% of all cases of diabetes, with a prevalence of 2-6% of adults in most western societies, a majority of which are overweight or obese. Weight loss in obese patients reduces the risk of developing diabetes by >50%. This thesis has investigated the first part of a two-stage therapeutic intervention against obesity in which adipose tissue lipolysis will be combined with increased energy expenditure: the approach is also designed to consider agents that will benefit glycaemic control in coexistent obesity and diabetes by improving insulin sensitivity. Rodent and human in vitro models of adipocyte biology and skeletal muscle have been developed, characterised and evaluated. They include isolated epididymal and parametrial adipocytes of lean and obese diabetic ob/ob mice, cultured 3T3-Ll preadipocytes, isolated human omental and subcutaneous adipocytes and rat L6 cultured muscle cells. Compounds investigated for anti-obesity and anti-diabetic properties include M2 (sibutramine metabolite), 3-guanidinopropionic acid and mazindol. In vivo studies were undertaken to investigate these compounds further in lean and ob/ob mice. In vivo studies indicated that M2 and 3-guanidinopropionic acid reduced body weight gain in ob/ob mice. The three compounds increased lipolysis in adipocytes isolated from lean and ob/ob mice and human adipose depots. The direct action of these compounds was mediated via a pathway involving the f3 adrenoceptors and components of the lipolytic signalling pathway, including protein kinase A and p38 MAP kinase. In addition, M2 and mazindol were capable of increasing glucose uptake into insulin sensitive tissues. M2 and mazindol can act directly on adipose tissue and skeletal muscle to increase glucose uptake via a pathway involving new protein synthesis and activation of the glucose transporters. The M2-stimulated pathway is activated by the conversion of phosphatidylinositol bisphosphate to phosphatidylinositol trisphosphate by phosphatidylinositol 3-kinase. Thus, M2, mazindol and 3-GPA showed pharmacodynamic properties which suggested they might be potential therapeutic treatments for obesity and diabetes.

Plasma irisin levels predict telomere length in healthy adults

The ageing process is strongly influenced by nutrient balance, such that modest calorie restriction (CR) extends lifespan in mammals. Irisin, a newly described hormone released from skeletal muscles after exercise, may induce CR-like effects by increasing adipose tissue energy expenditure. Using telomere length as a marker of ageing, this study investigates associations between body composition, plasma irisin levels and peripheral blood mononuclear cell telomere length in healthy, non-obese individuals. Segmental body composition (by bioimpedance), telomere length and plasma irisin levels were assessed in 81 healthy individuals (age 43∈±∈15.8 years, BMI 24.3∈±∈2.9 kg/m2). Data showed significant correlations between log-transformed relative telomere length and the following: age (p∈<∈0.001), height (p∈=∈0.045), total body fat percentage (p∈=∈0.031), abdominal fat percentage (p∈=∈0.038) , visceral fat level (p∈<∈0.001), plasma leptin (p∈=∈0.029) and plasma irisin (p∈=∈0.011), respectively. Multiple regression analysis using backward elimination revealed that relative telomere length can be predicted by age (b∈=∈-0.00735, p∈=∈0.001) and plasma irisin levels (b∈=∈0.04527, p∈=∈0.021). These data support the view that irisin may have a role in the modulation of both energy balance and the ageing process. © 2014 The Author(s).

Induction of lipolysis in vitro and loss of body fat in vivo by zinc-alpha(2)-glycoprotein

Loss of adipose tissue in cancer cachexia has been associated with tumour production of a lipid-mobilizing factor (LMF) which has been shown to be homologous with the plasma protein zinc-a2-glycoprotein (ZAG). The aim of this study was to compare the ability of human ZAG with LMF to stimulate lipolysis in vitro and induce loss of body fat in vivo, and to determine the mechanisms involved. ZAG was purified from human plasma using a combination of Q Sepharose and Superdex 75 chromatography, and was shown to stimulate glycerol release from isolated murine epididymal adipocytes in a dose-dependent manner. The effect was enhanced by the cyclic AMP phosphodiesterase inhibitor Ro20-1724, and attenuated by freeze/thawing and the specific ß3-adrenoreceptor antagonist SR59230A. In vivo ZAG caused highly significant, time-dependent, decreases in body weight without a reduction in food and water intake. Body composition analysis showed that loss of body weight could be attributed entirely to the loss of body fat. Loss of adipose tissue may have been due to the lipolytic effect of ZAG coupled with an increase in energy expenditure, since there was a dose-dependent increase in expression of uncoupling protein-1 (UCP-1) in brown adipose tissue. These results suggest that ZAG may be effective in the treatment of obesity.

Effect of maternal protein restriction during pregnancy and postweaning high-fat feeding on diet-induced thermogenesis in adult mouse offspring

Purpose: Prenatal undernutrition followed by postweaning feeding of a high-fat diet results in obesity in the adult offspring. In this study, we investigated whether diet-induced thermogenesis is altered as a result of such nutritional mismatch. Methods: Female MF-1 mice were fed a normal protein (NP, 18 % casein) or a protein-restricted (PR, 9 % casein) diet throughout pregnancy and lactation. After weaning, male offspring of both groups were fed either a high-fat diet (HF; 45 % kcal fat) or standard chow (C, 7 % kcal fat) to generate the NP/C, NP/HF, PR/C and PR/HF adult offspring groups (n = 7-11 per group). Results: PR/C and NP/C offspring have similar body weights at 30 weeks of age. Postweaning HF feeding resulted in significantly heavier NP/HF offspring (P <0.01), but not in PR/HF offspring, compared with their chow-fed counterparts. However, the PR/HF offspring exhibited greater adiposity (P <0.01) v the NP/HF group. The NP/HF offspring had increased energy expenditure and increased mRNA expression of uncoupling protein-1 and β-3 adrenergic receptor in the interscapular brown adipose tissue (iBAT) compared with the NP/C mice (both at P <0.01). No such differences in energy expenditure and iBAT gene expression were observed between the PR/HF and PR/C offspring. Conclusions: These data suggest that a mismatch between maternal diet during pregnancy and lactation, and the postweaning diet of the offspring, can attenuate diet-induced thermogenesis in the iBAT, resulting in the development of obesity in adulthood. © 2014 Springer-Verlag Berlin Heidelberg.

Television Watching, Diet Quality, and Physical Activity and Diabetes among Three Ethnicities in the United States

Diabetes is a world-wide epidemic associated with multiple environmental factors. Prolonged television viewing (TV) time has been related to increased risk of obesity and type 2 diabetes in several studies. TV viewing has been positively associated with cardiovascular disease risk factors, lower energy expenditure, over-eating high-calorie and high-fat foods. The objective of this study was to assess the associations of hours of TV viewing with dietary quality, obesity and physical activity for three ethnic minorities with and without type 2 diabetes. Diet quality and physical activity were inversely related to prolonged TV viewing. African Americans and participants with type 2 diabetes were more likely to watch more than 4 hours of TV per day as compared to their counterparts. Diet quality was inversely associated with physical activity level. Future studies are needed to establish the risk factors of prolonged TV watching in adult populations for the development of diabetes or diabetes-related complications. Although strategies to reduce TV watching have been proven effective among children, few trials have been conducted in adults. Intervention trials aimed at reducing TV viewing targeting people with type 2 diabetes may be beneficial to improve dietary quality and physical activity, which may reduce diabetes complications.

Television Watching, Diet Quality, Physical Activity and Diabetes Among Three Ethnicities in the United States

Diabetes is a world-wide epidemic associated with multiple environmental factors. Prolonged television viewing (TV) time has been related to increased risk of obesity and type 2 diabetes in several studies. TV viewing has been positively associated with cardiovascular disease risk factors, lower energy expenditure, over-eating high-calorie and high-fat foods. The objective of this study was to assess the associations of hours of TV viewing with dietary quality, obesity and physical activity for three ethnic minorities with and without type 2 diabetes. Diet quality and physical activity were inversely related to prolonged TV viewing. African Americans and participants with type 2 diabetes were more likely to watch more than 4 hours of TV per day as compared to their counterparts. Diet quality was inversely associated with physical activity level. Future studies are needed to establish the risk factors of prolonged TV watching in adult populations for the development of diabetes or diabetes-related complications. Although strategies to reduce TV watching have been proven effective among children, few trials have been conducted in adults. Intervention trials aimed at reducing TV viewing targeting people with type 2 diabetes may be beneficial to improve dietary quality and physical activity, which may reduce diabetes complications.

Arquitetura bioclimática para instituição de ensino fundamental em São Gonçalo do Amarante/RN

In the design of a building process must consider climatic variations in the region, the external conditions and the use of available resources in nature, like the sun, vegetation, rain and winds, to provide a built environment with comfort and environment reduced energy expenditure. However, increasing urbanization, often with an occupancy of disordered ground comes disregarding this knowledge and disregarding local characteristics, drastically reducing the green areas. This disordered occupation associated with the reduction of green spaces, is modifying aspects of climate and thus, damaging the thermal comfort of users. Given this situation was born the question: What projetuais strategies can bring better thermal conditions to an educational building located in a region of hot and humid weather? Thus, faced with two important issues , education and environmental comfort , the research is justified by the fact that there is a large national demand for expansions and renovations in its public schools , but not in most areas provides students with quality for good learning development. This paper aims to draw up a project for establishment of Primary Education with the application of the concepts of bioclimatic, highlighting the use of vegetation as a regulatory element of the climate. Initially we carried out a literature search; we analyzed architectural solutions and set up the site. The next phases, called understanding, were raised with the laws, rules and environmental restrictions. Subsequently, the program needs and the development of architectural design was defined. The conclusion of this paper presents the definition of criteria and solutions for the use of vegetation to design of bioclimatic architecture in hot and humid climates and contributes a catalog of plant species for schools in the metropolitan region of Natal, RN.

Age, body mass, mass change and dispersal distance of suckling and weaned grey seal (Halichoerus grypus) pups

Grey seal, Halichoerus grypus, pups in the breeding colony at Froan, Norway, have a bimodal pattern of early aquatic behaviour. About 40% of the pups spend their time ashore to save energy, which can be allocated to growth or deposition of energy-rich adipose tissue. The other 60% of the pups enter the sea during suckling and the early postweaning period, and disperse to other locations within the breeding colony. Pups may swim distances up to 12 km. Neonatal aquatic dispersal behaviour may lead to increased energy expenditure for thermoregulation and swimming, and thus lead to a low rate of body mass gain during suckling and a high rate of body mass loss after weaning. Thus, we examined relationships between natal aquatic dispersal behaviour and change in body mass (DeltaBM) in suckling and weaned pups. Suckling pups that had dispersed >2000 m had a significantly lower DBM than suckling pups that dispersed <2000 m or that did not disperse. In weaned pups, there were no effects of aquatic dispersal behaviour on DBM. We suggest that the bimodal natal aquatic dispersal behaviour in grey seals at the study site reflects two different strategies for postweaning survival: to stay ashore and get fat, or to take a swim and acquire diving and feeding skills.

Le rôle des acides gras oméga-3 sur la balance énergétique, la régulation de l’appétit, l’état émotionnel et l’implication du récepteur GPR120

L’obésité est un facteur de risque lié à des problèmes physiques, émotionnels et comportementaux. Aujourd’hui, l’alimentation est composée d’un régime typiquement occidental «Western diet» qui est riche en acides gras saturés (AGS) et pauvre en acides gras polyinsaturés (AGPI) tel que les oméga-3 (N-3) et occasionnant un déséquilibre du ratio alimentaire N-6/N-3. Ce déséquilibre est une des causes de la prévalence des maladies mentales y compris celles des troubles de l'humeur et de l’anxiété. L’acide docosahexaénoïque (ADH, 22: 6 n-3) est l’acide gras (AG) le plus abondant dans le cerveau et son accumulation est particulièrement élevée pendant la période périnatale. Il joue un rôle important dans le développement neuronal et d'autres fonctions du cerveau tel l'apprentissage et la mémoire. Des perturbations de l’environnement périnatal peuvent influencer à très long terme l’avenir de la descendance en la rendant plus susceptible de développer des problèmes d’obésité dans un contexte nutritionnel riche. On ignore cependant si le déficit alimentaire chez la mère et particulièrement en ADH aura un impact sur la motivation alimentaire de la progéniture. L’objectif principal de cette thèse est d’étudier le rôle potentiel des N-3 sur la balance énergétique, la motivation alimentaire, la dépression et le niveau d’anxiété des descendants de souris mâles adultes assujetties à une alimentation riche en gras. Nos données ont démontré qu‘un régime maternel déficitaire en ADH durant la période périnatale incitait la descendance à fournir plus d’effort afin d’obtenir un aliment palatable. Ceci entraînerait un dérèglement de l’homéostasie énergétique en augmentant le gain de poids et en diminuant l’activité locomotrice tout en exacerbant le comportement de type anxieux dès que les souris sont exposées à un milieu obésogène. Les acides gras libres (AGL) sont des nutriments essentiels fonctionnant comme des molécules de signalisation dans le cerveau en ayant des récepteurs qui jouent un rôle important dans le contrôle du métabolisme énergétique. Parmi eux, on distingue un récepteur couplé à la protéine G (GPCR), le GPR120. Ce récepteur activé par les AGPI ω-3 intervient dans les mécanismes anti-inflammatoires et insulino-résistants via les N-3. Une mutation dans le gène GPR120 occasionnée par une réduction de l’activité de signalisation du gène est liée à l’obésité humaine. L'objectif premier de cette deuxième étude était d’évaluer l'impact de la stimulation pharmacologique de GPR120 dans le système nerveux central (SNC) sur l'alimentation, les dépenses d'énergie, le comportement de type anxieux et la récompense alimentaire. Nos résultats démontrent qu’une injection centrale aiguë d'agoniste GPR120 III réduit la prise alimentaire ad libitum et la motivation alimentaire pour un aliment riche en gras et en sucre; ainsi que les comportements de type anxieux. L’injection centrale chronique (21 jours) de ce même agoniste GPR120 III transmis par une pompe osmotique a démontré que les souris placées sous diète hypercalorique (HFD n’ont présenté aucune modification lors de la prise alimentaire ni de gain de poids mais qu’il y avait comparativement au groupe de véhicule, une réduction du comportement de type anxieux, que ce soit dans le labyrinthe en croix surélevé (LCS) ou dans le test à champ ouvert (OFT). L’ADH est reconnu pour ses propriétés anorexigènes au niveau central. De plus, la stimulation des récepteurs de GPR120 au niveau du cerveau avec un agoniste synthétique peut produire un effet intense intervenir sur le comportement lié à l'alimentation des rongeurs. Trouver une approche visant à contrôler à la fois la neuroinflammation, la récompense alimentaire et les troubles émotionnels aiderait assurément au traitement de l'obésité et du diabète de type 2.

La perception du temps et sa modulation par la température chez les guêpes parasitoïdes

Les modèles d'optimalité postulent que les animaux en quête de ressources utilisent le taux de gain de valeur adaptative pour optimiser plusieurs comportements tels que la répartition du temps lors de l’exploitation d‘un agrégat et l'investissement en progénitures. Bien que la durée de plusieurs comportements doit être régulée, peu d’évidences de la perception du temps sont actuellement disponibles pour les insectes et aucune pour les guêpes parasitoïdes, et ce malgré leur importance en tant que modèles écologiques. De plus, puisque les guêpes parasitoïdes sont poïkilothermes, cette capacité pourrait être affectée par la température. Nous avons supposé que les guêpes parasitoïdes auraient la capacité de percevoir le temps, à la fois de façon prospective (mesure du temps écoulé) et rétrospective (durée d'un événement passé), afin d'optimiser les décisions liées à l'exploitation d’agrégats d’hôtes et à la reproduction. Nous avons également émis l'hypothèse que la température aurait une incidence sur la perception du temps des guêpes parasitoïdes. Pour la mesure prospective du temps, nous avons utilisé la capacité d’apprentissage associatif de Microplitis croceipes (Hymenoptera: Braconidae). Les guêpes ont été entraînées à associer une odeur à la durée d'un intervalle entre des hôtes. Après leur entraînement, elles ont été testées dans un tunnel de vol avec un choix d’odeurs. Les guêpes ont choisi majoritairement l'odeur associée à l'intervalle de temps auquel elles étaient testées. Nous avons également investigué le rôle de la dépense énergétique sur la mesure du temps. Suite à une restriction de mouvement des guêpes pendant l'intervalle de temps entre les hôtes, elles choisissaient aléatoirement dans le tunnel de vol. L'absence de dépense énergétique les aurait rendues incapables de mesurer le temps. La dépense d'énergie est donc un substitut essentiel pour mesurer le temps. Pour la mesure rétrospective du temps, nous avons utilisé le processus d'évaluation de l'hôte de Trichogramma euproctidis (Hymenoptera: Trichogrammatidae). Certains trichogrammes utilisent la durée du transit initial sur l'œuf hôte afin d’en évaluer la taille et d’ajuster le nombre d’œufs à y pondre. Nous avons augmenté artificiellement la durée de transit initiale de T. euproctidis en suspendant l'œuf hôte pour le faire paraître plus gros qu'un œuf de taille similaire. Une augmentation de la durée de transit initiale a augmenté la taille de la ponte. Ceci démontre la capacité de T. euproctidis de mesurer la durée du transit initial, et donc d’une mesure du temps rétrospective. Pour déterminer si la température modifie la mesure du temps dans les espèces poïkilothermes, nous avons utilisé le comportement d’exploitation d’agrégats d’hôtes de T. euproctidis. Les modèles d’optimalités prédisent que les guêpes devraient rester plus longtemps et quitter à un faible taux de gain de valeur adaptative suite à un déplacement de longue durée plutôt que pour un déplacement de courte durée. Nous avons testé l'impact d'un déplacement de 24 h à différentes températures sur l'exploitation d’agrégats d’hôtes. Un déplacement à température chaude augmente le temps de résidence dans l’agrégat et diminue le taux de gain de valeur adaptative au moment de quitter ; ces comportements sont associés à un trajet de longue durée. L'inverse a été observé lors d’un déplacement à une température froide. Les températures chaude et froide ont modulé la mesure du temps en accélérant ou ralentissant l'horloge biologique, faisant paraître le déplacement respectivement plus long ou plus court qu’il ne l’était réellement. Ces résultats démontrent clairement que les guêpes parasitoïdes ont la capacité de mesurer le temps, autant rétrospectivement que prospectivement. Des preuves directes de leur capacité sont maintenant disponibles pour au moins deux espèces de guêpes parasitoïdes, une composante essentielle des modèles d'optimalité. Le rôle de la dépense énergétique dans la mesure du temps a aussi été démontré. Nos résultats fournissent également la preuve de l'impact de la température sur la perception du temps chez les insectes. L'utilisation de la dépense énergétique en tant que proxy pour mesurer le temps pourrait expliquer une partie de sa thermosensibilité, puisque les guêpes parasitoïdes sont poïkilothermes. Cette mesure du temps sensible à la température pourrait affecter des stratégies de lutte biologique. Sur le terrain, au début de la journée, la température de l'air sera similaire à la température de l'air autour des plantes infestées par des parasites, alors qu'elle sera plus chaude pendant la journée. En lutte biologique augmentative, les guêpes parasitoïdes libérées resteraient plus longtemps dans les agrégats d’hôtes que celles relâchées en début de journée.

Determination of a Total Body Model of Efficiency Applied to a Rowing Movement in Humans

Efficiency represents the ratio of work done to energy expended. In human movement, it is desirable to maximise the work done or minimise the energy expenditure. Whilst research has examined the efficiency of human movement for the lower and upper body, there is a paucity of research which considers the efficiency of a total body movement. Rowing is a movement which encompasses all parts of the body to generate locomotion and is a useful modality to measure total body efficiency. It was the aim of this research to develop a total body model of efficiency and explore how skill level of participants and assumptions of the modelling process affected the efficiency estimates Three studies were used to develop and evaluate the efficiency model. Firstly, the efficiency of ten healthy males was established using rowing, cycling and arm cranking. The model included internal work from motion capture and efficiency estimates were comparable to published literature, indicating the suitability of the model to estimate efficiency. Secondly, the model was developed to include a multi-segmented trunk and twelve novice and twelve skilled participants were assessed for efficiency. Whilst the efficiency estimates were similar to published results, novice participants were assessed as more efficient. Issues such as the unique physiology of trained rowers and a lack of energy transfers in the model were considered contributing factors. Finally the model was redeveloped to account for energy transfers, where skilled participants had higher efficiency at large workloads. This work presents a novel model for estimating efficiency during a rowing motion. The specific inclusion of energy transfers expands previous knowledge of internal work and efficiency, demonstrating a need to include energy transfers in the assessment of efficiency of a total body action.

Efeitos de um programa de exercício físico na capacidade funcional de idosos institucionalizados no Lar da 3ª idade Beiral: projeto de intervenção

Mestrado em Fisioterapia

Understanding and validating accelerometry as a measure of physical activity in children with intellectual disabilities

Background Physical activity in children with intellectual disabilities is a neglected area of study, which is most apparent in relation to physical activity measurement research. Although objective measures, specifically accelerometers, are widely used in research involving children with intellectual disabilities, existing research is based on measurement methods and data interpretation techniques generalised from typically developing children. However, due to physiological and biomechanical differences between these populations, questions have been raised in the existing literature on the validity of generalising data interpretation techniques from typically developing children to children with intellectual disabilities. Therefore, there is a need to conduct population-specific measurement research for children with intellectual disabilities and develop valid methods to interpret accelerometer data, which will increase our understanding of physical activity in this population. Methods Study 1: A systematic review was initially conducted to increase the knowledge base on how accelerometers were used within existing physical activity research involving children with intellectual disabilities and to identify important areas for future research. A systematic search strategy was used to identify relevant articles which used accelerometry-based monitors to quantify activity levels in ambulatory children with intellectual disabilities. Based on best practice guidelines, a novel form was developed to extract data based on 17 research components of accelerometer use. Accelerometer use in relation to best practice guidelines was calculated using percentage scores on a study-by-study and component-by-component basis. Study 2: To investigate the effect of data interpretation methods on the estimation of physical activity intensity in children with intellectual disabilities, a secondary data analysis was conducted. Nine existing sets of child-specific ActiGraph intensity cut points were applied to accelerometer data collected from 10 children with intellectual disabilities during an activity session. Four one-way repeated measures ANOVAs were used to examine differences in estimated time spent in sedentary, moderate, vigorous, and moderate to vigorous intensity activity. Post-hoc pairwise comparisons with Bonferroni adjustments were additionally used to identify where significant differences occurred. Study 3: The feasibility on a laboratory-based calibration protocol developed for typically developing children was investigated in children with intellectual disabilities. Specifically, the feasibility of activities, measurements, and recruitment was investigated. Five children with intellectual disabilities and five typically developing children participated in 14 treadmill-based and free-living activities. In addition, resting energy expenditure was measured and a treadmill-based graded exercise test was used to assess cardiorespiratory fitness. Breath-by-breath respiratory gas exchange and accelerometry were continually measured during all activities. Feasibility was assessed using observations, activity completion rates, and respiratory data. Study 4: Thirty-six children with intellectual disabilities participated in a semi-structured school-based physical activity session to calibrate accelerometry for the estimation of physical activity intensity. Participants wore a hip-mounted ActiGraph wGT3X+ accelerometer, with direct observation (SOFIT) used as the criterion measure. Receiver operating characteristic curve analyses were conducted to determine the optimal accelerometer cut points for sedentary, moderate, and vigorous intensity physical activity. Study 5: To cross-validate the calibrated cut points and compare classification accuracy with existing cut points developed in typically developing children, a sub-sample of 14 children with intellectual disabilities who participated in the school-based sessions, as described in Study 4, were included in this study. To examine the validity, classification agreement was investigated between the criterion measure of SOFIT and each set of cut points using sensitivity, specificity, total agreement, and Cohen’s kappa scores. Results Study 1: Ten full text articles were included in this review. The percentage of review criteria met ranged from 12%−47%. Various methods of accelerometer use were reported, with most use decisions not based on population-specific research. A lack of measurement research, specifically the calibration/validation of accelerometers for children with intellectual disabilities, is limiting the ability of researchers to make appropriate and valid accelerometer use decisions. Study 2: The choice of cut points had significant and clinically meaningful effects on the estimation of physical activity intensity and sedentary behaviour. For the 71-minute session, estimations for time spent in each intensity between cut points ranged from: sedentary = 9.50 (± 4.97) to 31.90 (± 6.77) minutes; moderate = 8.10 (± 4.07) to 40.40 (± 5.74) minutes; vigorous = 0.00 (± .00) to 17.40 (± 6.54) minutes; and moderate to vigorous = 8.80 (± 4.64) to 46.50 (± 6.02) minutes. Study 3: All typically developing participants and one participant with intellectual disabilities completed the protocol. No participant met the maximal criteria for the graded exercise test or attained a steady state during the resting measurements. Limitations were identified with the usability of respiratory gas exchange equipment and the validity of measurements. The school-based recruitment strategy was not effective, with a participation rate of 6%. Therefore, a laboratory-based calibration protocol was not feasible for children with intellectual disabilities. Study 4: The optimal vertical axis cut points (cpm) were ≤ 507 (sedentary), 1008−2300 (moderate), and ≥ 2301 (vigorous). Sensitivity scores ranged from 81−88%, specificity 81−85%, and AUC .87−.94. The optimal vector magnitude cut points (cpm) were ≤ 1863 (sedentary), ≥ 2610 (moderate) and ≥ 4215 (vigorous). Sensitivity scores ranged from 80−86%, specificity 77−82%, and AUC .86−.92. Therefore, the vertical axis cut points provide a higher level of accuracy in comparison to the vector magnitude cut points. Study 5: Substantial to excellent classification agreement was found for the calibrated cut points. The calibrated sedentary cut point (ĸ =.66) provided comparable classification agreement with existing cut points (ĸ =.55−.67). However, the existing moderate and vigorous cut points demonstrated low sensitivity (0.33−33.33% and 1.33−53.00%, respectively) and disproportionately high specificity (75.44−.98.12% and 94.61−100.00%, respectively), indicating that cut points developed in typically developing children are too high to accurately classify physical activity intensity in children with intellectual disabilities. Conclusions The studies reported in this thesis are the first to calibrate and validate accelerometry for the estimation of physical activity intensity in children with intellectual disabilities. In comparison with typically developing children, children with intellectual disabilities require lower cut points for the classification of moderate and vigorous intensity activity. Therefore, generalising existing cut points to children with intellectual disabilities will underestimate physical activity and introduce systematic measurement error, which could be a contributing factor to the low levels of physical activity reported for children with intellectual disabilities in previous research.

Le rôle des acides gras oméga-3 sur la balance énergétique, la régulation de l’appétit, l’état émotionnel et l’implication du récepteur GPR120

L’obésité est un facteur de risque lié à des problèmes physiques, émotionnels et comportementaux. Aujourd’hui, l’alimentation est composée d’un régime typiquement occidental «Western diet» qui est riche en acides gras saturés (AGS) et pauvre en acides gras polyinsaturés (AGPI) tel que les oméga-3 (N-3) et occasionnant un déséquilibre du ratio alimentaire N-6/N-3. Ce déséquilibre est une des causes de la prévalence des maladies mentales y compris celles des troubles de l'humeur et de l’anxiété. L’acide docosahexaénoïque (ADH, 22: 6 n-3) est l’acide gras (AG) le plus abondant dans le cerveau et son accumulation est particulièrement élevée pendant la période périnatale. Il joue un rôle important dans le développement neuronal et d'autres fonctions du cerveau tel l'apprentissage et la mémoire. Des perturbations de l’environnement périnatal peuvent influencer à très long terme l’avenir de la descendance en la rendant plus susceptible de développer des problèmes d’obésité dans un contexte nutritionnel riche. On ignore cependant si le déficit alimentaire chez la mère et particulièrement en ADH aura un impact sur la motivation alimentaire de la progéniture. L’objectif principal de cette thèse est d’étudier le rôle potentiel des N-3 sur la balance énergétique, la motivation alimentaire, la dépression et le niveau d’anxiété des descendants de souris mâles adultes assujetties à une alimentation riche en gras. Nos données ont démontré qu‘un régime maternel déficitaire en ADH durant la période périnatale incitait la descendance à fournir plus d’effort afin d’obtenir un aliment palatable. Ceci entraînerait un dérèglement de l’homéostasie énergétique en augmentant le gain de poids et en diminuant l’activité locomotrice tout en exacerbant le comportement de type anxieux dès que les souris sont exposées à un milieu obésogène. Les acides gras libres (AGL) sont des nutriments essentiels fonctionnant comme des molécules de signalisation dans le cerveau en ayant des récepteurs qui jouent un rôle important dans le contrôle du métabolisme énergétique. Parmi eux, on distingue un récepteur couplé à la protéine G (GPCR), le GPR120. Ce récepteur activé par les AGPI ω-3 intervient dans les mécanismes anti-inflammatoires et insulino-résistants via les N-3. Une mutation dans le gène GPR120 occasionnée par une réduction de l’activité de signalisation du gène est liée à l’obésité humaine. L'objectif premier de cette deuxième étude était d’évaluer l'impact de la stimulation pharmacologique de GPR120 dans le système nerveux central (SNC) sur l'alimentation, les dépenses d'énergie, le comportement de type anxieux et la récompense alimentaire. Nos résultats démontrent qu’une injection centrale aiguë d'agoniste GPR120 III réduit la prise alimentaire ad libitum et la motivation alimentaire pour un aliment riche en gras et en sucre; ainsi que les comportements de type anxieux. L’injection centrale chronique (21 jours) de ce même agoniste GPR120 III transmis par une pompe osmotique a démontré que les souris placées sous diète hypercalorique (HFD n’ont présenté aucune modification lors de la prise alimentaire ni de gain de poids mais qu’il y avait comparativement au groupe de véhicule, une réduction du comportement de type anxieux, que ce soit dans le labyrinthe en croix surélevé (LCS) ou dans le test à champ ouvert (OFT). L’ADH est reconnu pour ses propriétés anorexigènes au niveau central. De plus, la stimulation des récepteurs de GPR120 au niveau du cerveau avec un agoniste synthétique peut produire un effet intense intervenir sur le comportement lié à l'alimentation des rongeurs. Trouver une approche visant à contrôler à la fois la neuroinflammation, la récompense alimentaire et les troubles émotionnels aiderait assurément au traitement de l'obésité et du diabète de type 2.