A atividade do complexo 1 da proteína alvo mecanístico da rapamicina (mTORC1), importante regulador da adiposidade e do metabolismo de lipídeos, está aumentada no tecido adiposo de camundongos obesos. A inibição completa de mTORC1 reduz a adiposidade, enquanto que sua inibição parcial potencializa a obesidade induzida por dieta. Assim, hipotetizamos que um nível ótimo de ativação de mTORC1 é necessário para promover aumento da adiposidade, de forma que sua superativação é tão inibitória para a deposição de gordura quanto sua inibição completa. Para testar esta hipótese, investigamos os efeitos da ativação constitutiva de mTORC1, induzida pela deleção de Tsc1, especificamente em adipócitos na adiposidade in vivo. A deleção de Tsc1 reduziu a massa do tecido adiposo visceral, mas não do subcutâneo, que foi associado ao aumento da lipólise e browning. Além disso, aumentou em ambos tecidos adiposos a massa e atividade oxidativa mitocondrial. Esses dados apoiam nossa hipótese de que é necessário um nível ótimo de ativação de mTORC1 para promover aumento da adiposidade. / The activity of mechanistic target of rapamycin complex 1 (mTORC1), an important regulator of adiposity and lipid metabolism, is increased in adipose tissue of obese mice. Complete mTORC1 inhibition reduces adiposity, whereas partial mTORC1 inhibition enhances diet-induced obesity. Therefore, we hypothesized that an optimal level of mTORC1 activity is required to increase adiposity, in such a manner that mTORC1 overactivation is as inhibitory to fat deposition as its complete inhibition. To test this hypothesis, we investigated the effects of constitutive mTORC1 activation, induced by Tsc1 deletion, specifically in adipocytes on adiposity in vivo. Tsc1 deletion reduced visceral, but not subcutaneous, fat mass, which was associated with increased lipolysis and browning. Moreover, it enhanced mitochondrial mass and oxidative activity in both visceral and subcutaneous fat. These data support our hypothesis that an optimal level of mTORC1 activation is necessary to increase adiposity.

A atividade do complexo 1 da proteína alvo mecanístico da rapamicina (mTORC1), importante regulador da adiposidade e do metabolismo de lipídeos, está aumentada no tecido adiposo de camundongos obesos. A inibição completa de mTORC1 reduz a adiposidade, enquanto que sua inibição parcial potencializa a obesidade induzida por dieta. Assim, hipotetizamos que um nível ótimo de ativação de mTORC1 é necessário para promover aumento da adiposidade, de forma que sua superativação é tão inibitória para a deposição de gordura quanto sua inibição completa. Para testar esta hipótese, investigamos os efeitos da ativação constitutiva de mTORC1, induzida pela deleção de Tsc1, especificamente em adipócitos na adiposidade in vivo. A deleção de Tsc1 reduziu a massa do tecido adiposo visceral, mas não do subcutâneo, que foi associado ao aumento da lipólise e browning. Além disso, aumentou em ambos tecidos adiposos a massa e atividade oxidativa mitocondrial. Esses dados apoiam nossa hipótese de que é necessário um nível ótimo de ativação de mTORC1 para promover aumento da adiposidade. / The activity of mechanistic target of rapamycin complex 1 (mTORC1), an important regulator of adiposity and lipid metabolism, is increased in adipose tissue of obese mice. Complete mTORC1 inhibition reduces adiposity, whereas partial mTORC1 inhibition enhances diet-induced obesity. Therefore, we hypothesized that an optimal level of mTORC1 activity is required to increase adiposity, in such a manner that mTORC1 overactivation is as inhibitory to fat deposition as its complete inhibition. To test this hypothesis, we investigated the effects of constitutive mTORC1 activation, induced by Tsc1 deletion, specifically in adipocytes on adiposity in vivo. Tsc1 deletion reduced visceral, but not subcutaneous, fat mass, which was associated with increased lipolysis and browning. Moreover, it enhanced mitochondrial mass and oxidative activity in both visceral and subcutaneous fat. These data support our hypothesis that an optimal level of mTORC1 activation is necessary to increase adiposity.

Les entreprises et plus généralement les organisations sont confrontées à des enjeux climatiques et économiques avec pour obligation de respecter un cadre légal et des orientations définis à des plus grandes échelles (régionale, nationale et internationale). Une organisation est souvent au fait du but ou de l’objectif à atteindre ; en revanche le moyen d’y parvenir peut nécessiter de l’apprentissage voire de la recherche. Le but de cette thèse est de fournir une méthodologie à l’usage des organisations pour réaliser le management stratégique des projets relatifs à leur transition énergétique. A partir de différents états de l’art sur la planification énergétique et la conception en particulier, nous avons pointé le déficit méthodologique auquel doit faire face une organisation : si les démarches et outils existent lorsqu’un problème est clairement identifié, comment justement identifier un ou des problèmes à partir uniquement d’une formulation de buts ou d’intentions ? La première partie propose une démarche de planification énergétique à l’échelle d’une organisation qui fait émerger, de manière structurée, les problèmes auxquels l’organisation sera potentiellement confrontée. Notre démarche repose sur l’utilisation des BEGES et des méthodes de management de l’énergie/GES d’une part, complétés par des démarches et outils de conception d’autre part. Ces derniers facilitent la consolidation des informations et des données nécessaires pour formuler et structurer les problèmes à résoudre. A l’issue de cette démarche certains problèmes sont formulés sous forme de contradictions et de conflits. La démarche développée est purement qualitative et adaptée au travail de groupe avec des experts. Cependant certaines données numériques traduisent des comportements de systèmes qui sont peu maitrisés par les parties prenantes du projet. La deuxième partie propose une méthode combinant la simulation et l’analyse de données pour identifier les contradictions d’objectifs et de cause qui peuvent ou semblent empêcher l’atteinte des objectifs. Ces contradictions sont formulées de sorte à pouvoir être traitées avec les méthodes de résolution de problèmes inventifs. Le principe d’identification des contradictions d’objectifs repose sur la transformation des réponses expérimentales ou de simulation des systèmes étudiés en données qualitatives binaires et sur l’identification des Paretos optimaux des données ainsi transformées. Les contradictions de causes concernent les facteurs ou paramètres de conception qui induisent les conflits d’objectifs. Nous proposons de les identifier à l’aide d’une méthode d’analyse discriminante binaire à base d’apprentissage supervisé associée à l’ANOVA. Nous montrons sur un cas d’étude, d’une part, comment intégrer cette approche dans la démarche présentée en partie 1 du mémoire, et d’autre part, comment l’utiliser pour obtenir des concepts de solutions dans un contexte multi-objectifs (diminution des consommations d’énergie, des émissions de GES, du coût etc.). / Companies and more generally organizations are confronted with climatic and economic issues, they have to respect a legal framework and orientations defined in larger scales (regional, national and international). An organization usually knows the goal or the objective to be achieved; however the way to do can require learning or even research. The goal of this thesis is to provide a methodology for the use of organizations to realize strategic management of their energy transition projects. From many different states of the art about energy planning and conception in particular, we show the methodological deficit which an organization has to face: if approaches and tools exist when a problem is clearly identified, how actually identify one or several problems from only a goal or intention formulation? The first part proposes an energy planning approach at an organizational scale to bring out in structured way problems which the organization may be confronted. Our approach is based on greenhouse gas emission assessments and energy/GHG management methods which are completed with conception approaches and some tools and methodologies. They facilitate the consolidation of required information and data to formulate and structure problems to solve. As a result of our approach some problems are formulated as contradictions and conflicts. The developed approach is purely qualitative and adapted to workgroup with experts. However some numerical data translate system behaviors which are sparsely mastered by project stakeholders. The second part proposes a combined method of simulation and data analysis to identify objective and cause contradictions which can or seem to prevent achieving the objectives. These contradictions are formulated in such a way to be handled with methods of resolution of inventive problems. The identification of objective contradictions is based on the transformation of experimental or simulation answers of the studied systems in binary qualitative data and on the identification of optimal Pareto of the transformed data. Cause contradictions concern conception factors or parameters which induce objective conflicts. We suggest identifying these contradictions with a binary discriminant analysis method based on supervised learning associated with ANOVA. On one hand, we show on a study case how integrate this initiative into the presented approaches in part 1 and on the other hand, how use it to obtain solution concepts in a multi-objective context (energy consumptions, GHG emissions or cost reduction etc.).