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1

Pandi, Amir. « Synthetic Metabolic Circuits for Bioproduction, Biosensing and Biocomputation ». Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS331.

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La biologie synthétique est le domaine de la bioingénierie permettant de concevoir, de construire et de tester de nouveaux systèmes biologiques en réécrire le code génétique. Les circuits biologiques synthétiques sont des outils sophistiqués permettant de construire des réseaux biologiques pour des applications médicales, industrielles et environnementales. Cette thèse de doctorat porte sur le développement de voies métaboliques synthétiques conçues à l'aide d'outils informatiques. Ces voies métaboliques sont intégrées à la couche de régulation transcriptionnelle pour développer des biocircuits pour la bioproduction, la biodétection et la biocalcul dans des systèmes cellulaires et acellulaires. Les résultats obtenus durant cette thèse de doctorat révèlent le nouveau potentiel des voies métaboliques dans l'établissement de biocircuits synthétiques. Le volet bioproduction-biodétection de la thèse vise à développer un nouveau biocapteur pour un sucre rare utilisé pour améliorer l'activité catalytique d’enzyme dans la cellule (in vivo). Ce biocapteur a ensuite été implémenté dans un système acellulaire (in vitro) pour découvrir et optimiser le comportement de biocapteurs à base de répresseurs. Une fois optimisé en système acellulaire, notre biocapteur a été utilisé pour surveiller la production enzymatique de sucre rare. Le développement de biocapteurs procaryotes acellulaires, qui reposent principalement sur des répresseurs, permet d'accélérer et de rendre plus efficace le cycle “design-build-test” dans le prototypage des voies métaboliques dans les systèmes acellulaires. L'application de la biodétection des circuits métaboliques pour le diagnostic est la mise en œuvre et l'optimisation des transducteurs métaboliques dans le système acellulaire. Les transducteurs sont des voies métaboliques composées d'au moins une enzyme catalysant un métabolite indétectable en un inducteur transcriptionnel, augmentant ainsi le nombre de petites molécules biologiquement détectables. En tant que nouvelle approche pour effectuer des biocalculs, des circuits métaboliques ont été appliqués pour construire des additionneurs métaboliques et des perceptrons métaboliques. Dans la cellule, trois transducteurs métaboliques et un additionneur métabolique ont été construits et caractérisés. Les systèmes acellulaires permettent d’accélérer la caractérisation de circuits biologiques, de finement régler le niveau d’expression d’un ou plusieurs gènes et facilite l’expression de plusieurs plasmides simultanément. Ceci a permis de construire de multiples transducteurs pondérés et des additionneurs métaboliques. Le modèle basé sur des données expérimentales a permis de concevoir un perceptron métabolique pour construire des classificateurs binaires à quatre entrées. Les additionneurs, perceptrons et classificateurs peuvent être utilisés dans des applications avancées telles que la détection de précision et dans le développement de souches pour le génie métabolique ou la thérapeutique intelligente
Synthetic biology is the field of engineerable life science and technology to design-build-test novel biological systems through reprogramming the code of DNA. Synthetic biocircuits are sophisticated tools to reconstruct biological networks for medical, industrial, and environmental applications. This doctoral thesis focuses on the development of synthetic metabolic pathways designed by computer-aided tools integrated with the transcriptional regulatory layer enabling bioproduction, biosensing, and biocomputation in whole-cell and cell-free systems. The achievements of this doctoral thesis bring attention to new potentials of metabolic pathways in the development of synthetic biocircuits. The bioproduction-biosensing section of the thesis is to build a novel sensor for a rare sugar used to improve the catalytic activity of its producing enzyme in the whole-cell system (in vivo). This sensor was then implemented in a TX-TL cell-free system (in vitro) as a proof of concept of a repressor based biosensor to discover and optimize the behavior of repressor based biosensors in the cell-free system that suffer from low fold repression. The optimized cell-free biosensor was then used to monitor the enzymatic production of the rare sugar. The development of cell-free prokaryotic biosensors which are mostly relying on repressors enables faster and more efficient design-build-test cycle in metabolic pathways prototyping in cell-free systems. The biosensing application of the metabolic circuits for diagnosis is the implementation and optimization of cell-free metabolic transducers. The transducers are metabolic pathways composed of at least one enzyme catalyzing an undetectable metabolite to a transcriptional inducer, hence expanding the number of biologically detectable small molecules in cell-free systems. Finally, as a radical approach to perform biocomputation, metabolic circuits were applied to build metabolic adders and metabolic perceptrons. In whole-cell system, three metabolic transducers and a metabolic adder (multiple transducers receiving multiple input metabolites and transform them into a common metabolite) were built and characterized. By taking advantage of cell-free systems in rapid characterization, high tunability, and the possibility of using tightly controlled multiple DNA parts, multiple weighted transducers and metabolic adders were implemented. The integrated model trained on the experimental data enabled the designing of a metabolic perceptron for building four-input binary classifiers. The adders, perceptrons and classifiers can be applied in advanced applications such as multiplex detection/precision medicine and in the development of designer strains for metabolic engineering or smart therapeutics
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Koch, Mathilde. « Computational modeling to design and analyze synthetic metabolic circuits ». Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS467/document.

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Les buts de cette thèse sont doubles, et concernent les circuits métaboliques synthétiques, qui permettent de détecter des composants chimiques par transmission de signal et de faire du calcul en utilisant des enzymes. La première partie a consisté à développer des outils d’apprentissage actif et par renforcement pour améliorer la conception de circuits métaboliques et optimiser la biodétection et la bioproduction. Pour atteindre cet objectif, un nouvel algorithme (RetroPath3.0) fondé sur une recherche arborescente de Monte Carlo guidée par similarité est présenté. Cet algorithme, combiné à des règles de réaction apprises sur des données et des niveaux différents de promiscuité enzymatique, permet de focaliser l’exploration sur les composés et les chemins les plus prometteurs en bio-rétrosynthèse. Les chemins obtenus par rétrosynthèse peuvent être implémentés dans des cellules ou des systèmes acellulaires. Afin de concevoir le meilleur milieu pour optimiser la productivité du système, une méthode d’apprentissage actif qui explore efficacement l’espace combinatoire des composants du milieu a été développée.La deuxième partie a consisté à développer des méthodes d’analyse, pour générer des connaissances à partir de données biologiques, et modéliser les réponses de biocapteurs. Dans un premier temps, l’effet du nombre de copies de plasmides sur la sensibilité d’un biocapteur utilisant un facteur de transcription a été modélisé. Ensuite, en utilisant des systèmes acellulaires qui permettent un meilleur contrôle des variables expérimentales comme la concentration d’ADN, l’utilisation des ressources a été modélisée pour assurer que notre compréhension actuelle des phénomènes sous-jacents est suffisante pour rendre compte du comportement du circuit, en utilisant des modèles empiriques ou mécanistiques. Couplés aux outils de conception de circuits métaboliques, ces modèles ont ensuite permis de développer une nouvelle approche de calcul biologique, appelée perceptrons métaboliques.Dans l’ensemble, cette thèse présente des outils de conception et d’analyse pour les circuits métaboliques synthétiques. Ces outils ont été utilisés pour développer une nouvelle méthode permettant d’effectuer des calculs en biologie synthétique
The aims of this thesis are two-fold, and centered on synthetic metabolic circuits, which perform sensing and computation using enzymes.The first part consisted in developing reinforcement and active learning tools to improve the design of metabolic circuits and optimize biosensing and bioproduction. In order to do this, a novel algorithm (RetroPath3.0) based on similarity-guided Monte Carlo Tree Search to improve the exploration of the search space is presented. This algorithm, combined with data-derived reaction rules and varying levels of enzyme promiscuity, allows to focus exploration on the most promising compounds and pathways for bio-retrosynthesis. As retrosynthesis-based pathways can be implemented in whole cell or cell-free systems, an active learning method to efficiently explore the combinatorial space of components for rational media optimization was also developed, to design the best media maximizing cell-free productivity.The second part consisted in developing analysis tools, to generate knowledge from biological data and model biosensor response. First, the effect of plasmid copy number on sensitivity of a transcription-factor based biosensor was modeled. Then, using cell-free systems allowing for broader control over the experimental factors such as DNA concentration, resource usage was modeled to ensure our current knowledge of underlying phenomenons is sufficient to account for circuit behavior, using either empirical models or mechanistic models. Coupled with metabolic circuit design, those models allowed us to develop a new biocomputation approach, called metabolic perceptrons.Overall, this thesis presents tools to design and analyse synthetic metabolic circuits, which are a novel way to perform computation in synthetic biology
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Audet, Diane. « Metabolic cost of aerobic dance circuit training ». Thesis, McGill University, 1992. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=56816.

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This study was undertaken to characterize the oxygen consumption and heart rate responses of subjects during laboratory simulated aerobic dance circuit training sessions. Sixteen female subjects performed six randomly assigned 30-minute aerobic dance circuit training protocols. Oxygen consumption and heart rate responses were monitored in response to changes in three independent variables which were: interval duration, leg involvement and fitness level. Results revealed that the different interval durations generated significantly different oxygen costs. Also, it was found that in relative terms (% of max VO$ sb2$), the low fitness group (max VO$ sb2 $ 45 ml/kg.min). Furthermore, it was found that the involvement of deep knee bends during the resistance training segment of the circuit significantly increased the oxygen cost when the resistance training segments were compared. Finally, the results showed that exercise intensity was overestimated when using percentage of max HR.
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Prudente, Paulo Adriano Naves. « Efeito do exercício combinado de intensidade moderada nos fatores de risco cardiometabólicos em mulheres com e sem síndrome metabólica ». Universidade Federal de Goiás, 2016. http://repositorio.bc.ufg.br/tede/handle/tede/6529.

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Introduction: The phenomenon of metabolic syndrome (MS) is associated with a set of factors that constitute cardiometabolic risk, among them are the increase in abdominal fat, dyslipidemia, hyperglycemia and hypertension. Exercise can contribute to change the picture of the metabolic syndrome, however the type of exercise, the volume and intensity ideals are not yet fully established. Objective: Analyze the effects of 24 weeks of combined exercise on cardiometabolic risk factors in women with no metabolic syndrome. Methods: The study is not a randomized experimental trial and not controlled with the participation of 36 sedentary women, divided into two groups, one with metabolic syndrome (CSM, n = 22) and one without (SSM, n = 14). Sociodemographic data were collected at the beginning. Anthropometric and cardiometabolic risk factors evaluations were performed before and after the exercises. The diagnosis of metabolic syndrome was based on IDF parameters. For the assessment of cardiometabolic risk were considered the following factors: waist circumference (WC), ratio waist / height (WHtR), systolic blood pressure (SBP) and diastolic (DBP), HDL-C, triglycerides (TGL), blood glucose fasting, fasting insulin and HOMA-IR. The participants underwent 24 weeks of combined exercise (resistance circuit + aerobic) of moderate intensity, verified by the perceived exertion, and performed with the use of low-cost equipment. Statistical analyzes were performed to compare the difference of the average values of cardiometabolic risk factors before and after exercise. Results: Comparing the groups, the CSM showed a significant reduction of the values of body mass (p = 0.02), BMI (p = 0.02), SBP (p = 0.01), DBP (p <0.001), WHtR (p <0.001). The SSM group showed no statistically significant changes in any of the cardiometabolic risk factors after the practice of combined exercises. Conclusion: We conclude that the combined exercises resulted in significant reductions and clinically positive for SBP and DBP in the CSM group
Introdução: O fenômeno da síndrome metabólica (SM) está associado a um conjunto de fatores que constituem riscos cardiometabólicos, dentre eles estão o aumento de gordura abdominal, a dislipidemia, a hiperglicemia e a hipertensão arterial sistêmica. O exercício físico pode contribuir para alterar o quadro da síndrome metabólica, entretanto o tipo de exercício, o volume e a intensidade ideais ainda não estão claramente estabelecidos. Objetivo: Analisar os efeitos de 24 semanas de exercícios físicos combinados nos fatores de risco cardiometabólicos em mulheres com e sem síndrome metabólica. Métodos: O estudo é um estudo experimental não randomizado e não controlado com participação de 36 mulheres sedentárias, alocadas em dois grupos, um com síndrome metabólica (CSM, n=22) e outro sem (SSM, n=14). Dados sóciodemográficos foram coletados no início. As avaliações antropométricas e dos fatores de riscos cardiometabólicos foram realizadas antes e após a prática dos exercícios. O diagnóstico da síndrome metabólica foi realizado com base nos parâmetros da IDF. Para a avaliação do riscos cardiometabólicos consideraram-se os seguintes fatores: circunferência da cintura (CC), relação cintura/estatura (RCE), pressão arterial sistólica (PAS) e diastólica (PAD), HDL-c, triglicerídeos (TGL), glicemia de jejum, insulina em jejum e o HOMA-IR. As participantes foram submetidas à 24 semanas de exercício combinado (resistido em circuito + aeróbio) de intensidade moderada, verificada por meio da percepção subjetiva de esforço, e realizados com a utilização de equipamentos de baixo custo. Foram realizadas análises estatísticas para comparar a diferença dos valores médios dos fatores de riscos cardiometabólicos antes e após os exercícios. Resultados: Na comparação entre os grupos, o CSM apresentou redução significativa para os valores da massa corporal (p=0,02), IMC (p=0,02), PAS (p=0,01), PAD (p<0,001), RCE (p<0,001). O grupo SSM não apresentou alterações estatisticamente significativas em nenhum dos fatores de riscos cardiometabólicos após a prática de exercícios combinados. Conclusão: Concluímos que os exercícios combinados resultaram em reduções significativas e clinicamente positivas para a PAS e PAD no grupo CSM.
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Farris, Gregory D. Kreider Richard B. « Analysis of exercise intensity and energy expenditure of women participating in the Curves exercise program ». Waco, Tex. : Baylor University, 2006. http://hdl.handle.net/2104/4198.

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LÓPEZ, LUJÁN MARÍA DEL CARMEN. « Development of a mobile open-circuit system based on indirect calorimetry for energetic metabolism studies in small ruminants ». Doctoral thesis, Universitat Politècnica de València, 2016. http://hdl.handle.net/10251/50430.

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[EN] For many years energy needs of ruminants have tried to be known to formulate rations adjusted, but it has been found that there are a variety of factors that affect them. Therefore, lots of studies are needed for evaluating the effect of these factors. Consequently, the main objective of this Thesis was to design and validate a respirometry system based on indirect calorimetry, which would allow assessing energy needs of small ruminants accurately. It was intended from the beginning it was a mobile system and of relatively low cost. Furthermore, a methane gas analyzer was incorporated to this system, which allowed the measurement of emissions of this greenhouse gas and quantification of energy losses in the form of methane. Initially the system had connected a mask, which was placed on the animal's face. A sample of exhaled gas was stored in a gas collection bag which was connected to the analyzer, and it measured the concentration of O2, CO2 and CH4 from the air. The proper functioning of the system was checked by a pilot experiment with dry Murciano-Granadina breed goats fed at maintenance level. Later this system was improved. Some of the most important changes were the replacement of the mask by a head hood in which the animal introduced the whole head, and the development of software that recorded and kept automatically concentrations of O2, CO2 and CH4 in exhaled air. This improvement allowed gas measurements during longer periods of time and recording more data. These changes were also validated through a pilot test with dry Manchega breed sheep. Subsequently, three experiments were performed. One of them with dry Guirra ewes and the other two with Murciano-Granadina goats during mid lactation. Diets were mixed rations that differed in the inclusion of cereal or fibrous by-products. In these experiments the effect of diet was studied on digestibility, energy balance and carbon-nitrogen, oxidation of nutrients, rumen parameters and methane production; in the case of lactating goats, also on milk performance. The determination of the calibration factor for O2 (1.005 ± 0.0101) confirmed the proper functioning of equipment. Moreover, small differences between the heat production obtained by indirect calorimetry and the carbon-nitrogen balance (2% in sheep and 1% in goats) demonstrated that this system allows determining the heat production of the animals reliably and accurately. In the experiments of this Thesis have been estimated maintenance energy needs of two Spanish native sheep breeds, such as the sheep from the Guirra and Manchega breeds; net maintenance requirements were 270 kJ/kg BW0.75, on average. In the case of Murciano-Granadina breed goats, in the middle of lactation, the average utilization efficiency of metabolizable energy for lactation was 0.61.
[ES] Desde hace años se ha tratado de conocer las necesidades energéticas de los rumiantes con el fin de formular raciones ajustadas, pero se ha comprobado que hay una gran variedad de factores que les afectan; por ello son necesarios estudios que evalúen el efecto de estos factores. Como consecuencia, el principal objetivo de esta tesis fue diseñar y validar un equipo de respirometría, basado en calorimetría indirecta, que permitiese evaluar las necesidades en energía de pequeños rumiantes de forma precisa. Se pretendió desde el inicio que fuese un sistema móvil y de relativo bajo coste. Además, a este sistema también se le incorporó un analizador de gas metano, que permitía la medición de las emisiones de este gas de efecto invernadero y la cuantificación de las pérdidas energéticas en forma de metano. Inicialmente el equipo tenía conectada una máscara que se colocaba en la cara del animal. Una muestra del gas espirado era almacenada en una bolsa de recogida de gases que era conectada al analizador, el cual medía la concentración de O2, CO2 y CH4 del aire. Se comprobó el correcto funcionamiento del sistema mediante una prueba piloto con cabras de raza Murciano-Granadina secas, alimentadas a nivel de mantenimiento. Posteriormente este sistema fue mejorado. Algunos de los cambios más importantes fueron la sustitución de la máscara por una urna en la que el animal introducía la cabeza entera, y el desarrollo de un software que registraba y guardaba de forma automática las concentraciones de O2, CO2 y CH4 del aire espirado. Esta mejora permitía medidas de gases durante periodos de tiempo más largos y el registro de muchos más datos. Estas modificaciones también fueron validadas mediante una prueba piloto con ovejas de raza Manchega secas. Posteriormente se realizaron tres experimentos. Uno de ellos con ovejas de raza Guirra secas y los otros dos con cabras Murciano-Granadinas en mitad de lactación. Las dietas fueron raciones mixtas que diferían en la inclusión de cereal o subproductos fibrosos. En estos experimentos se estudió el efecto de la dieta sobre la digestibilidad, balances de energía y carbono-nitrógeno, oxidación de los nutrientes, parámetros del rumen y producción de metano; en el caso de las cabras en lactación, también sobre los rendimientos productivos. La determinación del factor de calibrado para el O2 (1,005 ± 0,0101) confirmó el buen funcionamiento del equipo. Por otro lado, las pequeñas diferencias entre la producción de calor obtenida mediante calorimetría indirecta y el balance de carbono-nitrógeno (2% en ovejas y 1% en cabras) demostraron que este sistema permite determinar la producción de calor de los animales de forma fiable y precisa. En los trabajos de esta Tesis se han estimado las necesidades energéticas de mantenimiento en dos razas de ovejas autóctonas españolas, como son las razas Guirra y Manchega; las necesidades netas de mantenimiento fueron 270 kJ/kg PV0,75, de media. En el caso del ganado caprino de raza Murciano-Granadina, en mitad de lactación, la eficacia media de utilización de la energía metabolizable para la lactación fue de 0,61.
[CAT] Des de fa anys s'ha tractat de conèixer les necessitats energètiques dels remugants a fi de formular racions ajustades, però s'ha comprovat que hi ha una gran varietat de factors que els afecten; per això són necessaris estudis que avaluen l'efecte d'estos factors. Com a conseqüència, el principal objectiu d'aquesta Tesi va ser dissenyar i validar un equip de respirometría, basat en calorimetria indirecta, que permetera avaluar les necessitats en energia de menuts remugants de forma precisa. Es va pretendre des de l'inici que fóra un sistema mòbil i de relatiu baix cost. A més, a este sistema també se li va incorporar un analitzador de gas metà, que permetia el mesurament de les emissions d'este gas d'efecte hivernacle i la quantificació de les pèrdues energètiques en forma de metà. Inicialment l'equip tenia connectada una màscara que es col·locava en la cara de l'animal. Una mostra del gas expirat era emmagatzemada en una bossa d'arreplega de gasos que era connectada a l'analitzador, el qual mesurava la concentració d'O2, CO2 i CH4 de l'aire. Es va comprovar el funcionament correcte del sistema per mitjà d'una prova pilot amb cabres de raça Murciano-Granadina seques, alimentades a nivell de manteniment. Posteriorment este sistema va ser millorat. Alguns dels canvis més importants van ser la substitució de la màscara per una urna en què l'animal introduïa el cap sencera, i el desenrotllament d'un programari que registrava i guardava de forma automàtica les concentracions d'O2, CO2 i CH4 de l'aire expirat. Esta millora permetia mesures de gasos durant períodes de temps més llargs i el registre de moltes més dades. Estes modificacions també van ser validades per mitjà d'una prova pilot amb ovelles de raça Manxega seques. Després es van realitzar tres experiments. Un d'ells amb ovelles de raça Guirra seques i els altres dos amb cabres Murciano-Granadinas en mitat de lactació. Les dietes van ser racions mixtes que diferien en la inclusió de cereal o subproductes fibrosos. En estos experiments es va estudiar l'efecte de la dieta sobre la digestibilitat, balanços d'energia i carboni-nitrogen, oxidació dels nutrients, paràmetres del rumen i producció de metà; en el cas de les cabres en lactació, també sobre els rendiments productius. La determinació del factor de calibrat per a l'O2 (1,005 ± 0,0101) va confirmar el bon funcionament de l'equip. D'altra banda, les xicotetes diferències entre la producció de calor obtinguda per mitjà de calorimetria indirecta i el balanç de carboni-nitrogen (2% en ovelles i 1% en cabres) van demostrar que este sistema permet determinar la producció de calor dels animals de forma fiable i precisa. En els treballs d'esta Tesi s'han estimat les necessitats energètiques de manteniment en dos races d'ovelles autòctones espanyoles, com són les races Guirra i Manxega; les necessitats netes de manteniment van ser 270 kJ/kg PV0,75, de mitja. En el cas del bestiar caprí de raça Murciano-Granadina, en mitat de lactació, l'eficàcia mitjana d'utilització de l'energia metabolitzable per a la lactació va ser de 0,61.
López Luján, MDC. (2015). Development of a mobile open-circuit system based on indirect calorimetry for energetic metabolism studies in small ruminants [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/50430
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Fett, Carlos Alexandre. « "Avaliação metabólica nutricional de obesas no basal e após tratamento com dieta hipocalórica e treinamento em circuito ou caminhada" ». Universidade de São Paulo, 2005. http://www.teses.usp.br/teses/disponiveis/17/17138/tde-20052005-093115/.

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Propósito: Observar obesas pré e pós-dieta hipocalórica moderada, mais treinamento em circuito ou caminhada. quanto a variáveis nutricionais. Métodos: Grupos: treinamento em circuito, CIRC, n = 26, índice de massa corporal (IMC, kg/m2) = 33,2 ± 7,9 (Média±desvio padrão); idade = 32,6 ± 9,7 anos; e treinamento em caminhada, CAM, n = 24, IMC = 29,2±3,4; idade = 38,8 ± 10,5 anos. Avaliações: a composição corporal, coleta de urina e sangue, calorimetria indireta e testes físicos eram obtidos no inicio (M1) e final (M2) do estudo. Treinamento: mês 1 = 1 h x 3 d/semana; e mês 2 = 1 h x 4 d/semana. Dieta: foi adaptada do registro alimentar de uma semana, ajustado ao gasto energético de repouso (GER) e balanceada, com a seguinte proporção: 20% de proteínas; 20% de gorduras; e 60% de carbohidratos. Resultados: Pré-intervenção: 76% tinham algum familiar obeso; havia sintomatologia indicativa de: 60% ansiosas, 12% depressivas, 34% compulsivas e 32% distúrbio do sono, avaliadas por questionário no exame clínico. Foram encontrados níveis alterados de colesterol total (CT, mg/dL), e ou frações em 22% das sujeitas. O peso, IMC, o índice abdômem/quadril (IAQ), a soma de oito pregas cutâneas (SP8) se correlacionaram significativamente a quatro variáveis bioquímicas, e a circunferência do abdômen (CAb), e o percentual de gordura por antropometria (%GAntro) a cinco. Intervenção: O peso, IMC, %GAntro, endomorfia, massa gorda por bioimpedância (MGBia) e percentual de gordura por bioimpedância (%GBia), foram reduzidos significativamente nos dois grupos. O CIRC melhorou significativamente em todos (seis) e o CAM em três testes físicos. O CIRC teve significância para: ¯glicose (Gli), ¯AU, ¯CT, ¯Tg (todos em mg/dL), ­glóbulos vermelhos (GV) (mm3) e ­hematócrito (Ht) (%); e o CAM para: ¯Gli, ¯AU, ¯HDL, ­CT/HDL, ­GV, ­Ht. O GER não teve diferença em ambos os grupos. Conclusões: Pré-intervenção: Os dados antropometricos indicam boa correlação com os fatores bioquímicos de risco, mas não tem uma tendência constante. A taxa CT/HDL apresentou correlação com todas as medidas antropométircas e a Gli com nenhuma. A obesidade destas mulheres parece ter múltiplos fatores e o estilo de vida papel determinante. Intervenção: A atividade física per se foi importante para causar modificações nutricionais e da composição corporal nestas obesas. O CIRC teve melhor associação com o incremento da performance física e dados bioquímicos sanguineos e ambos os grupos preservaram o GER.
Purpose: To observe obese women before and after a low-calorie diet plus circuit training or jogging regarding nutritional parameters. Methods: Groups: circuit training, CIRC, n = 26, body mass index (BMI, kg/m2) = 33.2 ± 7.9 (Mean±SD), age = 32.6 ± 9.7 years; and jogging training, JOGG, n = 24, BMI = 29.2 ± 3.4; age = 38.8 ± 10.5 years. Evaluations: body composition, collection of urine and blood samples, indirect calorimetry and physical tests were performed at the beginning (M1) and at the end (M2) of the study. Training: month one: 1 h x 3 d/week; month two: 1 h x 4 d/week. Diet: was adapted on the basis of a one week feeding record feed and adjusted to the resting metabolic rate (RMR) measured by indirect calorimetry, with the following proportion: 20% protein, 20% fat; and 60% carbohydrate. Results: Pre-intervention: 76% had one or more obese family members; there were symptoms indicating that 60% were anxious, 12% depressive, 34% compulsive, and 32% had sleep disorders, evaluated by a questionnaire during clinical examination. Altered levels of total cholesterol (TC) and/or fractions were found in 22% of the subjects. Weight (W), BMI, waist/hip ratio (WHR), and the sum of eight skin folds (8SF), were significantly correlated with four biochemistry variables, and abdominal circumference (AbC), and anthropometric fat percentage (%FAnthro) were correlated with five. Intervention: Weight, BMI, %FAnthro, endomorphy, body fat mass by bioimpedance (BFMBia) and percent body fat by bioimpedance (%FBia) were reduced in both groups. CIRC significantly increased performance in all (six) tests and the JOGG in three physical tests. CIRC showed significant differences for: ¯glucose (Glu), ¯UA, ¯TC (TC), ¯Tg (all in mg/dL), ­red blood cells (RBC) (mm3) and ­hematocrit (Ht) (%); and JOGG for: ¯Glu, ¯UA, ¯HDL, ­CT/HDL, ­RBC, ­Ht. The RMR was not significantly reduced in both groups. Conclusions: Pre-intervention: Anthropometric data indicated a good correlation with biochemical factors, but did not show a constant tendency. CT/HDL showed correlation with all anthropometric measurements and Glu with none. The obesity of these women appears to have multiple factors, with life style playing a determinant role. Intervention: Physical activities were determined to favor body composition, reduced weight and blood markers. CIRC were better in terms of physical performance and blood markers. Both types of training were sufficient to prevent a fall of RMR.
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Lhomme, Tori. « La navette lactate tanycyte-neurone à POMC : un nouveau mécanisme de contrôle des circuits neuronaux de la prise alimentaire ». Thesis, Université de Lille (2018-2021), 2021. http://www.theses.fr/2021LILUS056.

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Les tanycytes du noyau arqué de l’hypothalamus (ARH) sont des cellules épendymogliales spécialisées se trouvant le long des parois du troisième ventricule (3V). Ils sont constitués d’un corps cellulaire polarisé dont la partie apicale entre en contact avec le liquide céphalo-rachidien (LCR) et dont la partie basale envoie un prolongement cytoplasmique vers les neurones du parenchyme nerveux. Leur localisation stratégique à l’interface entre le LCR contenant le glucose, et les neurones à pro-opiomélanocortine (POMC) répondant à des variations de glucose, renforce la possibilité que les tanycytes jouent un rôle important dans les mécanismes de détection hypothalamique du glucose, ainsi que dans le contrôle de la balance énergétique. Le but de ma thèse a été de tester l’hypothèse que les tanycytes de l’ARH formeraient un réseau métabolique de cellules interconnectées, au sein duquel le lactate, produit à partir du glucose circulant dans le LCR, diffuserait vers les neurones à POMC pour les alimenter en énergie, et les informer sur le statut glycémique de l’organisme afin de contrôler la balance énergétique. Les enregistrements électrophysiologiques ont indiqué qu’une majorité de neurones à POMC n’utilise pas le glucose, mais le lactate comme substrat énergétique pour soutenir leur activité électrique, via son métabolisme en pyruvate. Il a été montré que l’apport du lactate à ces neurones implique une navette fonctionnelle avec les tanycytes de l’ARH, dans laquelle ces derniers produisent le lactate à partir du glucose et le libèrent aux neurones à POMC via les transporteurs aux monocarboxylates (MCTs). De plus, les études ont démontré que la perturbation du réseau tanycytaire, formé par les connexines (Cxs) 43, conduit à une inhibition de l’activité électrique des neurones à POMC qui résulte d’un déficit de lactate dans l’ARH. De manière intéressante, il a été montré que le réseau tanycytaire contrôle la biodisponibilité du lactate dans cette région en réponse à des changements de taux circulants de glucose et régule le comportement alimentaire et le métabolisme énergétique chez les souris. Ces découvertes mettent en évidence un mécanisme utilisé par l’hypothalamus pour détecter les variations des taux circulants de glucose et pour maintenir la balance énergétique
Tanycytes of the arcuate nucleus of the hypothalamus (ARH) are specialized ependymoglial cells distributed along the lateral walls of the third ventricle (3V); their cell bodies contact the cerebrospinal fluid (CSF) while their processes arching in the tissue contact arcuate neurons. Their strategic location at the interface between the glucose-containing CSF and glucose-responsive proopiomelanocortin (POMC) neurons raises the possibility that tanycytes play a role in hypothalamic glucose detection mechanisms controlling energy balance. The aim of my thesis was to test the hypothesis that tanycytes convert glucose-containing CSF into lactate and distribute it to POMC neurons via a connexin 43 (Cx43)-mediated tanycytic metabolic networks, to control the energy balance. Electrophysiological recordings intriguingly indicated that most of the POMC neurons do not use glucose but lactate as energy substrate to sustain their electrical activity via its metabolism into pyruvate. The endogenous lactate required to sustain POMC neuronal activity is provided by ARH tanycytes via the conversion of glucose and shuttled to neurons via monocarboxylate transporters (MCTs). Furthermore, our study demonstrated that disruption of the Cx43-mediated tanycytic metabolic network leads to inhibition of POMC neuronal activity due to lactate deficiency into the ARH. These results thus show the importance of this network in the supply of lactate to POMC neurons. Finally, the tanycytic network was also shown to control the bioavailability of lactate in the ARH in response to changes in circulating glucose and to regulate feeding behavior and the energy metabolism in mice. Overall, our findings shed new lights on the mechanism used by the hypothalamus to monitor circulating levels of glucose and maintain of energy balance
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Bouffard, Marc. « Conception, modélisation et simulation in silico d'un nanosystème biologique artificiel pour le diagnostic médical ». Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS302/document.

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Le diagnostic médical, se fait traditionnellement, par l'examen des symptômes cliniques, puis en cherchant sur des prélèvements (sang, urine, biopsies, etc.) la présence (ou l'absence) simultanée des bio-marqueurs des diverses pathologies envisagées par le médecin. La recherche des bio-marqueurs se fait a l'aide d'équipements importants, dans un laboratoire d'analyse; les résultats étant communiqués au médecin, qui va les interpréter en appliquant un algorithme de diagnostic médical.Nous avons voulu regrouper dans un seul dispositif, pour une pathologie donnée, la détection des bio-marqueurs et une implémentation de l'algorithme de diagnostic approprié. La présence ou l'absence d'un bio-marqueur peut être représentée par une variable booléenne, et l'algorithme de diagnostic par une fonction booléenne complexe dont la valeur indiquera la présence de la pathologie ciblée.Notre dispositif de diagnostic sera un nano-calculateur biochimique artificiel dans lequel les informations logiques seront représentées par des métabolites et les calculs effectués par un réseau enzymatique synthétique. Pour réaliser ce calculateur, il a été nécessaire d'établir un fondement théorique des réseaux logiques enzymatiques. Nous avons ensuite utilisé cette théorie pour définir ce qu'est un circuit logique enzymatique et comment il calcule correctement la fonction booléenne associée. Pour des raisons de modularité et de réutilisabilité, nous avons décidé de concevoir des bibliothèques de portes logiques enzymatiques implémentant les opérateurs booléens de base, puis d'assembler ces briques de base pour obtenir le réseau enzymatique complet. J'ai donc conçu et développé deux outils logiciels, NetGate et NetBuild, qui vont réaliser automatiquement ces opérations.NetGate, qui va créer des bibliothèques contenant des centaines de portes logiques enzymatiques obtenues à partir de réseaux métaboliques d'organismes existants. Auparavant, il était nécessaire d'analyser manuellement ces réseaux métaboliques pour extraire chaque porte.NetBuild, qui va utiliser une bibliothèque de portes (par exemple créée par NetGate) et les assembler pour construire des circuits qui calculent une fonction booléenne donnée. Ces circuits utilisent comme entrées des métabolites spécifiques (par exemple: bio-marqueurs d'une pathologie) et produisent en sortie une espèce moléculaire facilement détectable (par colorimétrie par exemple)
The medical diagnosis is traditionally done by examining the clinical symptoms and by searching in samples (blood, urine, biopsies, etc.) for the simultaneous presence (or absence) of biomarkers of the various pathologies considered by the doctor. The search for biomarkers is conducted using large equipments in a specialised laboratory; The results being communicated to the doctor, who will then interpret them by applying a medical diagnostic algorithm.We wanted to combine in a single device, for a given disease, the detection of its biomarkers and an implementation of the appropriate diagnostic algorithm. The presence or absence of a biomarker can be represented by a boolean variable, and the diagnostic algorithm by a complex boolean function whose value indicates the presence of the targeted disease. Our diagnostic device is an artificial biochemical nano-computer in which logical information is represented by metabolites and the computations performed by a synthetic enzymatic network. To build this computer, it has been necessary to establish a theoretical basis of enzymatic logical networks. We then used this theory to define what an enzymatic logic network is, and how it computes correctly the associated boolean function. For modularity and reusability reasons, we decided to design libraries of enzymatic logic gates that implement basic boolean operators, and then to assemble these building blocks to get the complete logic enzymatic network. So, I have designed and developed two software tools, NetGate and NetBuild, which will automatically perform these operations.NetGate creates libraries containing hundreds of enzymatic logic gates obtained from the metabolic networks of living organisms. Before that, it was necessary to manually analyse these metabolic networks in order to extract each logic gate.NetBuild uses a library of logic gates (for example created using NetGate) and assembles them to build circuits that compute a given boolean function. These circuits use specific metabolites for its inputs (for example the biomarkers of a pathology) and produce a readily detectable molecular species (using colorimetry for example)
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Saucisse, Nicolas. « Dissection du rôle de la voie intracellulaire de mTORC1 dans les circuits hypothalamiques à la mélanocortine régulant la prise alimentaire ». Thesis, Bordeaux, 2016. http://www.theses.fr/2016BORD0151/document.

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L’hypothalamus est une structure cérébrale ayant un rôle clé dans la régulation de la prise alimentaire. Parmi les différentes populations neuronales qui le composent, les neurones produisant la pro-opiomélanocortine (POMC) sont classiquement connus pour diminuer la prise alimentaire et le poids corporel via la libération de neuropeptides produits par le clivage de POMC. Notre étude, grâce à l’utilisation d’approches génétiques, pharmacologiques, électrophysiologiques et moléculaires, remet en question les notions classiques sur la fonction des neurones à POMC dans la balance énergétique, en démontrant qu’il existe deux sous-populations fonctionnellement distinctes de neurones à POMC, qui augmentent ou diminuent la prise alimentaire en fonction du neurotransmetteur qu’elles libèrent, l’acide γ-aminobutyrique (GABA) ou le glutamate. Une troisième population capable de produire aussi bien du GABA que du glutamate a également été identifiée. La régulation des neurones à POMC GABAergiques et glutamatergiques dépend de la voie de la cible de la rapamycine chez les mammifères (mTORC1), qui fonctionne comme un détecteur d’énergie cellulaire, et du système endocannabinoïde (ECS), qui régule la libération de neurotransmetteurs. De plus, nous avons également démontré, via l’utilisation de souris mutantes conditionnelles, l’importance de la protéine p62 ou séquestrome 1 (p62/SQSTM1), qui régule l’activité de mTORC1 et l’autophagie, dans les neurones à POMC dans la régulation de l’homéostasie énergétique. Nos données offrent un nouvel aperçu sur les mécanismes moléculaires impliqués dans la régulation de la balance énergétique
The hypothalamus is a brain structure with a key role in the regulation of food intake. Among the different neuronal populations of which it is composed, pro-opiomelanocortin (POMC) neurons are classically known to decrease food intake and body weight through the release of neuropeptides produced by the cleavage of POMC. Our study, through the use of genetic, pharmacological, electrophysiological and molecular approaches, challenges conventional notions about POMC neuron function in energy balance by showing that there are two functionally distinct POMC neuronal sub-populations, which increase or decrease food intake depending on which neurotransmitter they release, γ-aminobutyric acid (GABA) or glutamate. A third population capable of producing both GABA and glutamate has also been identified. The regulation of POMC GABAergic and glutamatergic neurons depends on the mechanistic target of rapamycin complex 1 (mTORC1) pathway, which functions as a cellular energy sensor, and the endocannabinoid system (ECS), which regulates neurotransmitters release. In addition, we have also demonstrated through the use of a conditional knockout mice, the importance of the protein p62 or sequestrome 1 (p62/SQSTM1), which regulates mTORC1 activity and autophagy, in POMC neurons for the regulation of energy homeostasis. Our data provide new insights on the molecular mechanisms involved in the regulation of energy balance
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FONDI, MARCO. « Bioinformatics of genome evolution : from ancestral to modern metabolism ». Doctoral thesis, 2010. http://hdl.handle.net/2158/546258.

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YANG, CHIH-SHENG. « Discovery of a Novel Signaling Circuit Coordinating Drosophila Metabolic Status and Apoptosis ». Diss., 2011. http://hdl.handle.net/10161/5672.

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Apoptosis is a conserved mode of cell death executed by a group of proteases named caspases, which collectively ensure tissue homeostasis in multicellular organisms by triggering a program of cellular "suicide" in response to developmental cues or cellular damage.

Accumulating evidence suggests that cellular metabolism impinges directly upon the decision to initiate cell death. Several links between apoptosis and metabolism have been biochemically characterized. Using Xenopus oocyte extracts, our laboratory previously discovered that caspase-2 is suppressed by NADPH metabolism through an inhibitory phosphorylation at S164. However, the physiological relevance of these findings has not been investigated at the whole organism level. Studies presented in this dissertation utilize both Schneider's Drosophila S2 (S2) cells and transgenic animals to untangle the influence of metabolic status on fly apoptosis.

We first demonstrate a novel link between Drosophila apoptosis and metabolism by showing that cellular NADPH levels modulate the fly initiator caspase Dronc through its phosphorylation at S130. Biochemically and genetically blocking NADPH production removed this inhibitory phosphorylation, resulting in the activation of Dronc and the subsequent apoptotic cascade in cultured S2 cells and specific neuronal cells in transgenic animals. Similarly, non-phosphorylatable Dronc was found to be more potent than wild-type in triggering neuronal apoptosis. Moreover, upregulation of NADPH prevented Dronc-mediated apoptosis upon abrogation of Drosophila Inhibitor of Apoptosis (IAP) protein 1 (DIAP1) by double-stranded RNA (dsRNA) or cycloheximide (CHX) treatment, revealing a novel mechanism of DIAP1-independent apoptotic regulation in Drosophila. Mechanistically, the CaMKII-mediated phosphorylation of Dronc hindered its activation, but not its catalytic activity. As NADPH levels have been implicated in the regulation of oocyte death, we demonstrate here that a conserved regulatory circuit also coordinates somatic apoptosis and NADPH levels in Drosophila.

Given the regulatory role of NADPH in the activation of Dronc in Drosophila and caspase-2 in vertebrates, we then attempted to further elucidate the underlying signaling pathways. By tracking the catabolic fate of NADPH, we revealed that fatty acid synthase (FASN) activity was required for the metabolic suppression of Dronc, as both the chemical inhibitor orlistat and FASN dsRNA abrogated NADPH-mediated protection against CHX-induced apoptosis in S2 cells. Interestingly, it has been previously demonstrated that blocking FASN induces cell death in numerous cancers, including ovarian cancer; however, the mechanism is still obscure. As our results predict that suppression of FASN activity may prevent the inhibitory phosphorylation of Dronc and caspase 2 (at S130 and S164 respectively), we examined the contribution of caspase-2 to cell death induced by orlistat using ovarian cancer cells. Indeed, caspase-2 S164 was dephosphorylated upon orlistat treatment, initiating the cleavage and activation of caspase-2 and its downstream target, Bid. Knockdown of caspase-2 significantly alleviated orlistat-induced cell death, further illustrating its involvement.

Lastly, we developed an assay based on bimolecular fluorescence complementation (BiFC) to monitor the oligomerization of Dronc in S2 cells, a crucial step in its activation. The sensitivity of this assay has been validated with several apoptotic stimuli. A future whole-genome screen employing this assay is planned to provide new insights into this complex apoptotic regulatory network by unbiasedly identifying novel apoptotic regulators.


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Moore, Corona Sharlen Yared. « The role of oligodendrocytes in higher-order circuit functions ». Doctoral thesis, 2018. http://hdl.handle.net/11858/00-1735-0000-002E-E4F5-E.

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Liu, Yin-chieh, et 劉應傑. « Nucleus Accumbens Deep Brain Stimulation for Amelioration of Cognitive Impairment in Metabolic Syndrome Animal Model : Mitochondrial Biogenesis and Circuit Reanimation ». Thesis, 2019. http://ndltd.ncl.edu.tw/handle/6uuzzd.

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碩士
國立陽明大學
生物醫學工程學系
107
Cognitive function impairment was shown that associated with metabolic syndrome (MetS). Nucleus accumbens (NAc) was responsible for dopamine sensing and glucose metabolism which deep brain stimulation (DBS) at NAc could improve mitochondrial function in prefrontal cortex, whereas NAc-DBS for memory-related cognitive function was yet to be investigated. This study explored whether NAc-DBS changed mitochondria function of dopaminergic pathway in two species of mice, including C57BL/6 mice as wild-type (WT) mice and CCL5/RANTES knock out (k.o.) mice as MetS model. In WT mice, the ratio of oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) significantly increased in medial prefrontal cortex (mPFC) (p = 0.004) and ventral hippocampus (vHIPP) (p = 0.007), but decreased in NAc (p = 0.008) after NAc-DBS; phosphorylated 5' adenosine monophosphate-activated protein kinase (pAMPK) significantly decreased in mPFC (p = 0.006), NAc (p = 0.002) and VTA (p = 0.004); peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC-1α) significantly increased in mPFC (p = 0.006) and vHIPP (p = 0.020) with cognitive function improvement by novel object recognition test (NOR) (p = 0.009). In CCL5/RANTES k.o. mice, the OCR and ECAR significantly increased in mPFC (p = 0.012) and VTA (p = 0.007), but decreased in NAc (p = 0.016); the pAMPK significantly decreased in mPFC (p = 0.032), vHIPP (p = 0.027) and VTA (p = 0.002) but significantly increased in NAc (p = 0.032); the PGC-1α significantly increased in NAc (p = 0.042) and vHIPP (p = 0.008); the presynaptic protein, synaptophysin significantly increased in mPFC (p = 0.038), NAc (p = 0.021) and vHIPP (p = 0.041). In addition, cognitive function significantly improved in NOR (p = 0.042) and restored functional connectivity (FC) of dopaminergic pathway after NAc-DBS was reported (p < 0.05). Taken together, NAc-DBS improved cognitive function in both C57BL/6 and CCL5/RANTES mice, associating with improved metabolic function and mitochondrial biogenesis of dopaminergic pathway.
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Lee, Yuan-Xin, et 李元鑫. « A study of an intervention of the circuit exercise training to promote health-related physical fitness and quality of life for the people with metabolic syndrome ». Thesis, 2012. http://ndltd.ncl.edu.tw/handle/75166328766756299638.

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碩士
國立中正大學
運動與休閒教育研究所
100
The purpose of this study was to explore the effects of intervention of 12-weeks circuit exercise training on the health-related physical fitness and quality of life for the people with metabolic syndrome. The subjects were recruited by 121 patients with metabolic syndrome (age : 56.06 ± 13.69 years, height : 160.34 ± 8.07 cm, weight : 68.70 ± 12.19 kg) from the sports medicine center of the example of the hospital at Chia-Yi county. This study was applied by purposive sampling and divided to the experimental group (n = 86) and control group (n = 35). The experimental group had treated by 12 weeks circuit exercise training, 60 minutes per day, three days a week. The data were analyzed by descriptive statistics, t-test, and multiple regression analysis. The results of the study were found as follow : 1. In terms of demographic variables of the patients with metabolic Syndrome, most of subjects(70.2%) belonged to the elderly and higher, education level distribution of average(30%), unemployed 56%, married persons 80%, live with spouses and children 50%, gained wage mostly 33.9% , Buddhism religion mostly 45.5%, doing exercise behavior 60%, taking a nap 50%, drinking tea behavior 57%, drinking coffee behavior 30%, the few subject alcohol abuse(7.4%), smoking(9.1%), chewing betel nut(3.3%), vegetarian 10%, drug use 47%, the sleep time of most subject(57.9%) was 5-7 hours. 2. Regarding of the health-related physical fitness after 12-weeks circuit exercise training: there were an obvious improvement among body composition, cardiovascular, muscle strength, power, agility, reaction time, balance and flexibility. According to demography variables, the health-related physical fitness was made apparently progress. For example, the groups of non-drinking coffee, doing exercise behavior, sleep time 5-7 hours, higher education, under 66 years old, living with a spouse and children, taking a nap. 3. Regarding of the quality of life after 12-weeks circuit exercise training: it was a significant improvement included physical function(PF), general health(GH), vitality( VT), role emotional(RE), and mental component summary (MCS). Based on demography variables, the quality of life was made obviously progress. For example, the groups were included non-drinking coffee, doing exercise behavior, sleep time 5-7 hours, higher education, age between 66-80 years old, living with a spouse, taking a nap. 4. There was no significant correlation between health-related physical fitness and quality of life via the intervention of 12 weeks circuit exercise training, which was analyzed by multiple regression. Key words: circuit exercise training, health-related physical fitness, quality of life, metabolic syndrome
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