. "Thermogen\u00E8se" . . "Brown and beige thermogenic adipose tissues improve energetic homeostasis and represent a potential therapeutic targets for the treatment of obesity and aging associated metabolic diseases. Besides decades of research and the very well-described role of noradrenergic signaling, the mechanisms underlying their plasticity, activation and function are still poorly understood. In contrast to white adipose tissue that stores energy to make it available to the organism, brown adipose tissue dissipates energy as heat, and is involved in non-shivering thermogenesis. This metabolic specificity is permitted by brown adipocytes, which exhibit strong oxidative capacities due to their high content in mitochondria and the expression of the uncoupling protein 1 (UCP1). Beige adipocytes have similar metabolic characteristics but appear in specific regions of certain white adipose tissues by the browning phenomenon, following stimulation such as cold exposure. However, these cells appear in other stress situations, suggesting that they may have other functions than thermogenesis. My team's work has previously shown that lactate and ketone bodies, metabolites produced when substrate fluxes (glucose and fatty acids respectively) exceed oxidative capacities and act as regulators of redox metabolism through inter-cellular and inter-organ dialogues, are powerful inducers of browning. The induction of UCP1 by these metabolites is due to a redox mechanism (increase in NADH,H+/NAD+ ratio), and because UCP1 reduces this redox pressure by accelerating the respiratory chain, browning thus appears as an adaptive mechanism to maintain redox homeostasis. Because the underlying molecular mechanisms were poorly understood, my thesis objective was to characterize the expression of lactate transporters in adipocytes and to understand their role in their plasticity and metabolic activity. The fine mapping of the subcutaneous inguinal adipose tissue in mice, using laser microdissection experiments, gene expression measurement and confocal imaging, revealed i) a strong positive correlation between the expression of the lactate transporter Mct1 (monocarboxylate transporter 1) and that of Ucp1 and (ii) the appearance of UCP1 following cold exposure restricted to the subpopulation of adipocytes expressing MCT1 and pre-existing at thermoneutrality. These results highlight the MCT1 protein as a marker of dormant beige adipocytes, able of be activated during cold exposure. This finding is reinforced by the absence of the MCT1 protein in perigonadic adipose tissue which is resistant to browning, and its strong expression in classical brown adipocytes. While MCT1 is necessary for lactate-induced UCP1 expression, we showed that it was not involved in the Ucp1 regulation by adrenergic signaling. However, lactate oxidation and isotopic profiling experiments showed that MCT1 was essential for the metabolic activity of beige adipocytes, by controlling lactate export and import. Lactate export by MCT1 is necessary for glucose consumption, especially during \u00DF3 adrenergic agonist stimulation, by maintaining the redox NADH,H+/NAD+ ratio which is fundamental for the control of glycolysis. MCT1-dependent lactate import feeds the oxidative metabolism and kreb cycle of these cells. A genetically engineered mouse model showed that inducible MCT1 loss of function in adipocytes impact glycemia during cold exposure, confirming the crucial role of MCT1 and lactate fluxes in the control of glucose metabolism in brown/beige adipose tissues. The proposed mechanisms highlight the fundamental role of MCT1 in beige adipocytes biology and could be extrapolated to brown adipocytes." . "R\u00F4le des flux de lactate dans le m\u00E9tabolisme des tissus adipeux beiges et bruns" . "R\u00F4le des flux de lactate dans le m\u00E9tabolisme des tissus adipeux beiges et bruns" . . "Les tissus adipeux thermog\u00E9niques beiges et bruns am\u00E9liorent l'hom\u00E9ostasie \u00E9nerg\u00E9tique et repr\u00E9sentent des cibles th\u00E9rapeutiques potentielles pour traiter les maladies m\u00E9taboliques associ\u00E9es \u00E0 l\u2019ob\u00E9sit\u00E9 et au vieillissement. Malgr\u00E9 des d\u00E9cennies de recherche et le r\u00F4le tr\u00E8s bien d\u00E9crit de la signalisation noradr\u00E9nergique, les m\u00E9canismes sous-jacents \u00E0 leur plasticit\u00E9, leur activation et leur fonction restent encore mal compris. Contrairement au tissu adipeux blanc qui stocke l\u2019\u00E9nergie pour la mettre \u00E0 disposition de l'organisme, le tissu adipeux brun la dissipe sous forme de chaleur, et participe \u00E0 la thermog\u00E9n\u00E8se de non frisson. Cette sp\u00E9cificit\u00E9 m\u00E9tabolique est permise par les adipocytes bruns, aux fortes capacit\u00E9s oxydatives dues \u00E0 leur richesse en mitochondries et \u00E0 l\u2019expression de la prot\u00E9ine d\u00E9couplante UCP1 (Uncoupling Protein 1). Les adipocytes beiges pr\u00E9sentent des caract\u00E9ristiques m\u00E9taboliques similaires mais apparaissent dans des zones sp\u00E9cifiques de certains tissus adipeux blancs par le ph\u00E9nom\u00E8ne de brunissement, suite \u00E0 une stimulation comme l\u2019exposition au froid. Cependant, ces cellules apparaissent dans d\u2019autres conditions de stress, ce qui sugg\u00E8re qu\u2019elles puissent assurer d\u2019autres fonctions que la thermogen\u00E8se. Les travaux de mon \u00E9quipe ont montr\u00E9 que le lactate et les corps c\u00E9toniques, des m\u00E9tabolites produits lorsque les flux de substrats (glucose et acides gras respectivement) d\u00E9passent les capacit\u00E9s oxydatives et qui agissent comme des r\u00E9gulateurs du m\u00E9tabolisme redox au travers de dialogues inter-cellulaires et inter-tissulaires, sont de puissants inducteurs du brunissement. L\u2019induction d\u2019UCP1 par ces m\u00E9tabolites passe par un m\u00E9canisme d\u00E9pendant du potentiel red/ox (augmentation du ratio NADH,H+/NAD+), et comme UCP1 permet de diminuer ce potentiel red/ox en acc\u00E9l\u00E9rant le fonctionnement de la cha\u00EEne respiratoire, le brunissement appara\u00EEt comme un m\u00E9canisme adaptatif pour maintenir l\u2019hom\u00E9ostasie red/ox." . "Role of lactate fluxes in brown and beige adipose tissues metabolism" . . . "2020" . . . "M\u00E9tabolisme" . . "Tissu adipeux" . "Lactate" . "Text" . . "Glycolyse" . . "Transporteurs aux monocarboxylates (MCT)" . . . "Tissus adipeux beiges et bruns" . . "Red/ox" . . "Th\u00E8ses et \u00E9crits acad\u00E9miques" .