Les agrumes très consommés au niveau mondial, représente des sources de caroténoïdes tels que la β-cryptoxanthine, qui contribuent avec les flavonoïdes (hespéridine) aux effets santé de ces fruits et en particulier dans la prévention du diabète de type 2 (DT2). Le DT2 est une pathologie mondiale en croissance exponentielle. L’objectif général de ce travail est par conséquent d’étudier les propriétés nutrition-santé de concentrés de jus de clémentine, obtenus par une technologie membranaire innovante et spécifiquement enrichis en β-cryptoxanthine (βCX) et hespéridine (HES) mais également en pectines. Le devenir digestif de ces phytomicronutriments, garants de la qualité nutritionnelle des concentrés a évalué dans un premier temps en couplant le modèle de digestion in vitro aux cellules intestinales de type Caco-2. Pour une meilleure vision physiologique des mécanismes associés aux premières étapes de la digestion, des modèles de digestion, statique et dynamique, sont comparés. La bioaccessibilité et l’absorption intestinale des caroténoïdes sont fortement influencées par la teneur et structure des pectines. Dans un second temps, les activités biologiques (disglycémie, dislipidémie, inflammation) impliquées dans la prévention du DT2 sont évaluées in vivo chez le rat après administration du concentré d’agrume. L’étude a démontré qu'un aliment à base d'agrume spécifiquement enrichi en βCX et HES est efficace dans la prévention du syndrome métabolique/DT2, soulignant le rôle possible de la βCX et de sa bioconversion en rétinoïdes. Une étude in vitro complémentaire sur macrophages murins révèle des effets anti-inflammatoires synergiques des 2 phytomicronutriments. / Citrus fruits, which are widely consumed worldwide, represent sources of carotenoids such as βCX, which contribute with flavonoids (HES) to the health effects of these fruits, particularly in the prevention of type 2 diabetes (T2D). T2D is a worldwide pathology that is growing exponentially. The general objective of this work is therefore to study the nutritional and health properties of clementine juice concentrates obtained by innovative membrane technology and specifically enriched in both βCX and HES but also in pectins. The digestive behaviour of these phytomicronutrients, guarantors of the nutritional quality of the concentrates, was first assessed by coupling the in vitro digestion model with the Caco-2 intestinal cells. For a better physiological vision of the mechanisms associated with the first stages of digestion, models of static and dynamic digestion are compared. The bioavailability and intestinal absorption of carotenoids are strongly influenced by the content and structure of pectins. In a second step, the biological activities (disglycemia, dislipidemia, inflammation) involved in the prevention of T2D are evaluated in vivo in rat after administration of the citrus concentrate. The study demonstrated that a citrus food specifically enriched in βCX and HES is effective in preventing metabolic syndrome/T2D, highlighting the possible role of βCX and its retinoid bioconversion. A complementary in vitro study on murine macrophages reveals synergistic anti-inflammatory effects of the two phytomicronutrients.

La laine de verre est un matériau utilisé pour l'isolation acoustique et thermique des habitations. Ce matériau est constitué à 95% de fibres de verre et à 5% d'un liant. Bien que ce dernier soit utilisé en quantité très faible dans la formulation du matériau, il est responsable de l'obtention de bonnes propriétés mécaniques en assurant, notamment, l'intégrité structurelle du panneau de laine de verre. Pour préparer ces liants, une résine et des additifs (huile, silicone et silane) sont utilisés. Depuis une cinquantaine d'années, les résines majoritairement utilisées pour la préparation de liant pour la fabrication de la laine de verre sont de type formo-phénolique. Bien que les propriétés mécaniques des panneaux de laine de verre obtenus avec cette résine soient bonnes, il a été nécessaire d'éliminer le formaldéhyde, composé Cancérigène-Mutagène-Reprotoxique, de la formulation. C'est pourquoi de nouvelles résines ont dû être développées. Ces développements ont permis de retenir une résine pH-compatible à base de saccharose et avec des propriétés mécaniques analogues à celles obtenues avec la résine formo-phénolique. Le but de cette thèse est donc d'accéder à une connaissance approfondie des mécanismes réactionnels mis en jeu dans la formation de cette résine pour pouvoir, in fine, en optimiser ses performances / Glass wool is a material used for the acoustic and thermal insulation of dwellings. This material contains 95% of glass fibers and 5% of binder. Although this binder is used in a very small quantity in the formulation, it provides the expected mechanical properties by ensuring the structural integrity of the glass wool panel. To prepare these binders, resin and additives (oil, silicone and silane) are used. For fifty years the resins mostly used for the preparation of glass wool’s binders were the formo-phenolic’s types. Although theses resins provide good mechanical properties of the glass wool panels, it was necessary to remove the formaldehyde, a Carcinogen-Mutagen-Reprotoxic compound, from the formulation. As a consequence, new resins were developed. These developments helped us to retain a pH-compatible resin based on sucrose with mechanical properties as good as formo-phenolic’s resin. So, the aim of this thesis is to investigate the whole chemistry’s mechanism involved in the formation of this resin in order to be able to increase its performance

Le glycérol et le fructose sont des molécules qui peuvent être extraites facilement de labiomasse et en des quantités substantielles. Ce travail de recherche porte sur la déshydratationcomme moyen de valoriser ces composés. C’est dans ce but que des catalyseurs supportés suroxydes de zirconium et de titane, ainsi que des matériaux de type phosphate de calcium, ontété préparés et testés pour la réaction de déshydratation du glycérol en phase gazeuse. Desoxydes mixtes de niobium et cerium ainsi que des oxydes mixtes mésoporeux de Nb2O5-MeO2 (M = Ce, Zr, Ti) ont été également préparés et cette fois-ci testés pour la réaction dedéshydratation du fructose en milieu aqueux. Dans les deux cas, les propriétés acido-basiquesde surface des catalyseurs étudiés ont été corrélées à leur efficacité catalytique. / Glycerol and fructose are molecules that are readily available in substantial quantities fromthe biomass. In this work dehydration routes for valorization of these compounds wereinvestigated. Therefore, zirconia and titania based catalysts, and calcium phosphate materialswere prepared and evaluated in the glycerol dehydration in gas phase. Niobia-ceria mixedoxides and mesoporous Nb2O5-MeO2 (M = Ce, Zr, Ti) mixed oxides were prepared andtested in fructose dehydration reaction in aqueous phase. The surface acid-base properties ofthe studied catalysts were correlated to their catalytic performance.

Cette maitrise a été fait en co-direction : Jean-Marc Lavoie (UdeM) et David St-Pierre (UQAM). / Mise en contexte : La présente étude a pour but de tester l’hypothèse selon laquelle l’accumulation excessive de lipides au foie perturbe le métabolisme du cholestérol. La stéatose hépatique perturberait ainsi principalement les voies métaboliques qui impliquent les récepteurs de LDL au foie. Méthodologie: Des rats Wistar (n/groupe = 10) ont été soumis soit à une diète standard (SD), une diète enrichie en lipides (HFD : High Fat Diet) ou à une diète occidentale (WD : Western Diet) pour une durée de 2 ou 6 semaines. Au niveau de la composition des diètes, 60% de l’apport calorique de la diète enrichie en lipides provient des lipides tandis que la diète occidentale est composée à 40% de lipides et 35% de sucrose dont 17,5% de fructose. Résultats: Comparativement aux animaux traités pendant 2 semaines, le poids des tissus adipeux était environ trois fois plus élevé (~ 20 vs 7 g) chez les animaux soumis à 6 semaines de diètes obésogènes. Une augmentation significative du gain de poids (~ 40g) a été observée uniquement après 6 semaines chez les groupes soumis à la HFD ou la WD (P < 0.01). Comparativement aux animaux soumis à la diète conventionnelle, les niveaux de triglycérides (TG) hépatiques étaient significativement supérieurs chez les rats nourris avec la HFD et WD (P < 0.01) et ce, indépendamment de la durée du traitement. Après deux semaines, des concentrations de TG hépatiques significativement plus élevées (P < 0.05) ont été observés chez les animaux avec la WD comparativement à celles des rats avec la HFD. Des niveaux de cholestérol plasmatiques significativement plus élevés (P < 0.05) ont été mesurés chez les animaux avec la WD par rapport à la SD et la HFD et ce indépendamment de la durée. Après 2 et 6 semaines de diètes, l’expression génique au foie de LDL-R, PCSK9 et SREBP2, qui sont impliqués dans la captation des LDL-cholestérol, a significativement diminué chez les animaux soumis à la WD comparativement à ceux nourris avec la diète SD ou HFD (P < 0.01). De la même manière, des niveaux d’ARNm de LRP1 et ACAT2 significativement diminués (P < 0.01) ont été mesurés chez les animaux nourris avec WD comparativement ceux du groupe SD. L’expression de l’HMGCoAR, l’enzyme limitante impliquée dans la régulation de la synthèse endogène de cholestérol, a été significativement 6 diminuée chez les animaux soumis à la WD comparativement à ceux traités avec la SD ou la HFD après 2 (P < 0.001) et 6 semaines (P < 0.05). Dû au fait que la diète soit enrichie en sucrose et conséquemment en fructose, la WD a fortement favorisé l’expression de ChREBP et ACC, deux régulateurs majeurs dans la voie de la lipogenèse de novo. Conclusion: Ces résultats suggèrent que la diète de type occidentale augmenterait les niveaux de TG en favorisant simultanément la captation exogène de lipides ainsi que leur production endogène par l’activation de la lipogenèse de novo. L’altération de la voie de la captation du cholestérol par les LDL-R favoriserait une augmentation rapide des taux plasmatiques de cholestérol. / Background: The present study was designed to test the hypothesis that excessive fat accumulations impair cholesterol metabolism mainly through alterations in the LDL-receptor (LDL-R) pathway in liver. Method: Rats were either submitted to standard (SD), high fat (HFD; 60% kcal) or western (WD; 40% fat + 35% sucrose (17.5% fructose)) diets for 2 or 6 weeks. Results: Weight gain (~ 40g) was observed only following 6 weeks of the obesogenic diets (P < 0.01). Compared to the 2-week treatment, obesogenic diets tripled fat pad weight (~ 20 vs 7 g) after 6 weeks. Hepatic triglyceride (TG) levels were greater in response to both the WD and HFD compared to the SD (P < 0.01) at 2 and 6 weeks and their concentrations were greater (P < 0.05) in WD than HFD at 2 weeks. Plasma cholesterol levels were higher (P < 0.05) in animals submitted to WD compare to SD and HFD. After 2 and 6 weeks, liver expression of LDL-R, PCSK9 and SREBP2, involved in LDL-cholesterol uptake, was lower in animals submitted to WD than in others treated with HFD or SD (P < 0.01). Similarly, LRP1 and ACAT2 mRNA levels were lower (P < 0.01) among WD compared to SD-fed rats. Expression of the gene coding the main regulator of endogenous cholesterol synthesis, HMGCoAR was reduced in response to WD compared to SD and HFD at 2 (P < 0.001) and 6 (P < 0.05) weeks. Being enriched in fructose, the WD strongly promoted the expression of ChREBP and ACC, two key regulators of de novo lipogenesis. Conclusion: These results show that the WD promptly increased TG levels in the liver by potentiating dietary fat storage and de novo lipogenesis. This effect impaired hepatic cholesterol uptake via the LDL-R axis and promoted a rapid increase in plasma cholesterol levels.

Typescript (photocopy). / Digitized by Kansas Correctional Industries

A quantificação dos componentes bioquímicos como frutose, ácido cítrico e proteína total existentes no plasma seminal de caprinos e ovinos localizados na região Centro-Oeste do Brasil é uma forma de avaliar a atividade fisiológica e bioquímica espermáticas. Estes dados servem como indicadores de prováveis problemas com os testículos e glândulas acessórias desses animais e de sua respectiva fertilidade. A frutose e o ácido cítrico são importantes para o sêmen como fonte de energia metabólica e como componente de sistema tampão, respectivamente. A frutose é um marcador da função secretora das vesículas seminais, e é um componente importante para a sobrevivência dos espermatozóides em condições anaeróbicas e está estreitamente relacionada com a motilidade inicial das células espermáticas. Sendo assim, os objetivos do presente projeto foram analisar quantitativamente esses componentes do plasma seminal de bodes e carneiros sob latitude 20&deg;31\'S em quatro épocas do ano e purificar, através de técnicas cromatográficas, a enzima fosfolipase A2, importante proteína presente no plasma seminal. As análises bioquímicas foram feitas usando-se um espectrofotômetro UV/Vis para obtenção da curva padrão e para a determinação das concentraçõoes mensais e da concentração anual média dos constituintes analisados. A purificação da PLA2 foi feita por cromatografia líquida preparativa usando-se como fase estacionária a coluna Superdex 75-16/60 (GE HealthCare) de exclusão por tamanho e membranas semipermeáveis de 10 e 30 kDa. Como resultado das análises bioquímicas, obteve-se a concentração anual média de proteínas totais de 3,27 &plusmn; 0,60 g/dL para ovinos e de 5,02 &plusmn; 0,43 para caprinos, ácido cítrico de 1015,33 &plusmn; 66,50 µg/mL para ovinos e de 1584,35 &plusmn; 143,90 µg/mL para caprinos e frutose de 23,40 &plusmn; 4,80 mg/dL para ovinos e 72,73 &plusmn; 18,50 mg/dL para caprinos. Os resultados mostraram que a PLA2 extraída do plasma seminal de ovinos tem massa molecular próxima de 13,8 kDa e a PLA2 do plasma seminal de caprinos tem massa molecular próxima a 12,8 kDa. / Quantification of biochemical components in seminal plasma including fructose, citric acid and total protein of goat and sheep of the Midwest region of Brazil is one way of evaluating the biochemical and physiological activity of the sperm. These data serve as indicators of potential problems with the testicles and accessory glands of these animals and their relative fertility. The fructose and citric acid are important for the semen as a source of metabolic energy and as a component of a buffer, respectively. Fructose is a marker of secretory function of seminal vesicles, important for the survival of spermatozoa under anaerobic conditions, and is closely related to the initial motility of sperm cells. Therefore, the objectives of this project were to quantitatively analyze these components in the seminal plasma of goats and sheep in latitude 20&deg;31\'S 3 1\'S in four seasons and purify by chromatographic techniques the enzyme phospholipase A2, an important protein in the seminal plasma. Biochemical analysis were done using a spectrophotometer UV / Vis to obtaining the standard curve and to determine the monthly and annual average concentration of the constituents analyzed. The purification of PLA2 was performed by preparative liquid chromatography using the column as stationary phase Superdex 75-16/60 (GE HealthCare) by size exclusion and semipermeable membranes 10 and 30 kDa. As a result of biochemical analysis, we obtained the annual average concentration of total protein of 3,27 &plusmn; 0,60 g / dL for sheep and 5,02 &plusmn; 0,43 g/dL for goats, citric acid of 1015,33 &plusmn; 66, 50 g / mL for sheep and 1584,35 &plusmn; 143,90 g / mL for goats and fructose 23,40 &plusmn; 4,80 mg / dL for sheep and 72,73 &plusmn; 18,50 mg / dL for goats. The results showed that the PLA2 extracted from seminal plasma of sheep has a molecular mass of 13,8 kDa and the next PLA2 from goat seminal plasma has a molecular mass close to 12,8 kDa.

Introdução: A Síndrome Metabólica (MS) é uma comorbidade frequentemente encontrada nos pacientes que apresentam Doença Pulmonar Obstrutiva Crônica (DPOC). A DPOC e a MS possuem características em comum e o tabagismo é um fator de risco comum à DPOC e à MS. Apesar da intricada associação entre a DPOC e a MS, sabe-se muito pouco a respeito de como a co-ocorrência da MS afeta a resposta da DPOC ao treinamento físico - um tratamento efetivo para MS e que tem efeito protetor contra o enfisema induzido por tabaco - e à história natural desta. Objetivo: Avaliar como a ingestão crônica de frutose interfere na história natural e nos efeitos do treinamento físico aeróbio sobre a lesão pulmonar induzida por fumaça de cigarro. Métodos: Camundongos C57Bl/6 machos foram divididos em oito grupos (n=16-20/grupo): Controle, Fumo, Exercício, Fumo+Exercício, Frutose, Frutose+Fumo, Frutose+Exercício e Frutose+Fumo+Exercício; e expostos à fumaça de cigarro (30 minutos, 2x/dia), exercício físico (1 hora/dia) ou frutose (20% em água de beber) durante 12 semanas. Após o período de tratamento os animais foram anestesiados, submetidos à avaliação da mecânica respiratória e eutanasiados para coleta de sangue, lavado broncoalveolar (LBA), pulmões e músculos quadríceps para posteriores análises de histologia, dosagem de citocinas e avaliações de expressão gênica e estresse oxidativo. Resultados: A ingestão de frutose causou destruição do septo alveolar comparável com aquela causada pelo fumo (p < 0,001). A combinação de frutose e fumo produziu uma destruição alveolar mais severa do que qualquer um deles sozinho (p=0,008). O exercício físico inibiu o aumento do número total de células inflamatórias e macrófagos no LBA (p < 0,001), impediu o aumento dos níveis de interleucina (IL)-6, IL-10, IL-1beta, TNF-alfa, adiponectina e leptina no plasma e/ou músculo esquelético (p < 0,001), alterou a porcentagem de fibras colágenas e elásticas no parênquima pulmonar (p < 0,001) e atenuou o desenvolvimento do enfisema no grupo Frutose+Fumo+Exercício. Não houve efeito do exercício físico na mecânica respiratória, expressão de genes antioxidantes e estresse oxidativo. Conclusão: O treinamento físico aeróbio atenuou parcialmente o desenvolvimento do enfisema pulmonar em camundongos expostos à fumaça de cigarro e à frutose / Introduction: The Metabolic Syndrome (MS) is a comorbidity frequently presented by patients with Chronic Obstructive Pulmonary Disease (COPD). COPD shares with MS common features and tobacco use is a risk factor for both COPD and MS. Despite of this intricate association between COPD and MS, very little is known about how co-occurrence of MS might affect the response of COPD to physical exercise - an effective treatment for MS that has a protective effect against tobacco-induced COPD - and its natural history. Objective: To evaluate how chronic fructose intake interferes in the natural history and in the effects of aerobic exercise training on lung injury induced by exposure to CS. Methods: Male C57Bl/6 mice were assigned to 8 groups: Control, Smoke, Exercise, Smoke+Exercise, Fructose, Fructose+Smoke, Fructose+Exercise and Fructose+Smoke+Exercise (n=16-20/group) and treated accordingly with CS (30min twice/day), exercise training (1h/day) or fructose (20% in the drinking water) for 12 weeks. After the treatment period the animals were anesthetized, submitted to the evaluation of respiratory mechanics and were euthanized for collect of blood plasma, bronchoalveolar lavage fluid (BALF), lungs and quadriceps muscles for subsequent histology analysis and measures of cytokine levels, gene expression and oxidative stress. Results: Fructose ingestion caused destruction of alveolar septa comparable to that caused by the CS (p < 0,001). Combination of fructose and CS caused an alveolar destruction even more severe than either one alone (p=0,008). Exercise training inhibited the increase of the total number of inflammatory cells and macrophages in BALF (p < 0,001), inhibited the increase of the interleukin (IL)-6, IL-10, IL-1beta, TNF-alpha, adiponectin and leptin levels in plasma and/or skeletal muscle (p < 0,001), altered the percentage of collagen and elastic fibers in lung parenchyma (p < 0,001) and attenuated the development of emphysema in the Fructose+Smoke+Exercise group. There was no effect of exercise training on respiratory mechanics, antioxidant genes expression and oxidative stress. Conclusion: Aerobic exercise training partially attenuated the development of lung emphysema in mice exposed to cigarette smoke and fructose

Este trabalho descreve a preparação, a caracterização e o uso de um biossensor bienzimático confeccionado com as enzimas glicose oxidase e frutose dehidrogenase imobilizadas em camadas auto-organizadas ou self-assembled monolayers (SAMs) de cistamina para a quantificação de açúcares em alimentos. Após o preparo do eletrodo de ouro com a SAM de cistamina, biossensores foram construídos e para obtenção de melhores respostas, condições foram otimizadas, tais como: concentração do mediador tetratiafulvaleno (TTF), porcentagem de glutaraldeído, temperatura e tempo de vida do biossensor. Com as condições estabelecidas, fez-se então, a determinação analítica da D-glicose e da D-frutose em eletrólito puro pelo método da adição de padrão e os resultados foram obtidos por voltametria cíclica e cronoamperometria. A corrente de pico de oxidação do mediador de elétrons (TTF) aumentou proporcionalmente com o aumento da concentração e não ocorreram deslocamentos nos potenciais de pico. Os limites de detecção (LD) foram encontrados por meio do desvio padrão da média aritmética de dez amperogramas do branco no potencial equivalente aos dos picos de oxidação do mediador de elétrons TTF, juntamente com o valor do coeficiente angular da curva analítica. Após a obtenção da curva analítica o biossensor foi aplicado diretamente em amostras de refrigerante dietético e não dietético, bem como em amostras de adoçantes comerciais, onde foram realizados testes comparativos da resposta dos biossensores. Para o eletrólito puro e amostras de refrigerante dietético e de adoçantes, ou seja, onde não há presença de D-glicose e D-frutose, notou-se a ausência de corrente de pico, enquanto que para as amostras de refrigerante não dietético, houve um valor significativo de resposta de corrente, indicando a presença dos açúcares em estudo. Com o propósito de verificar a influência de interferentes e o efeito de matriz, foi construída uma curva analítica para a D-glicose e para a D-frutose, em amostras de refrigerante dietético e adoçantes, onde foram obtidas as menores quantidade destes açúcares. Para o refrigerante não dietético, foi determinado o valor inicial dos açúcares presentes nas amostras. Pode-se afirmar que a utilização dos biossensores baseados nas enzimas GOx e FDH mostraram-se eficientes para a determinação dos açúcares D-glicose e D-frutose nas amostras analisadas (com diferença significativa nos valores de corrente), apresentando uma resposta rápida, além da eliminação do efeito da matriz. A utilização do mediador de elétrons (TTF) possibilitou a reação em potencial próximo de zero, diminuindo o efeito de interferentes e evitando a desnaturação das enzimas. / This work describes the preparation, characterization and application of a bienzymatic biosensor based in the glucose oxidaze and fructose dehydrogenase immobilized on self-assembled monolayer of cystamine for sugar quantification in foodstuff. After the modification of the gold electrode with cystamine, the biosensors were developed and optimized for best responses. Optimization parameters were: mediator tetrathiafulvalene (TTF) concentration, glutaraldehyde percentage, temperature and life time of the biosensor. With the best conditions established, the analytical determinations of d-glucose and d-fructose in pure phosphate buffer were conducted by the standard additions method and the results obtained by cyclic voltammetry and chronoamperometry. The oxidation peak current related to the TTF voltammetric behavior raised proportionally to the increasing concentration of d-glucose or d-fructose, in a given and constant peak potential. The methodology detection limits were found using the standard deviation of ten chronoamperograms of the blank solution, in the potential value corresponding to that of TTF oxidation, and the slope of the analytical curve. After the analytical curve acquirement the biosensor was directly applied in samples of diet or non-diet softdrinks, as well as in commercial sweeteners samples, with comparative tests of the biosensor responses. For pure electrolyte and for diet foodstuff samples, i.e., were there is not expectation for d-glucose or d-fructose existence, it was detected the lack of the voltammetric peak associated with the mediator oxidation. In non-diet samples, a pronounced voltammetric peak was obtained, testifying the presence of sugar in the electrolytes under study. The matrix effect was verified by means of an analytical curve obtained for both analytes (d-glucose and d-fructose), in diet and sweeteners samples, properly spiked with known amounts of each analyte. It can be concluded that the utilization of the biosensor based in GOx and FDH showed to be efficient for d-glucose and d-fructose determinations in the analysed samples, with a fast response time and elimination of the matrix effect. The mediator promoted the electrochemical reaction to occur in potentials very close to zero, minimizing the interferences or the enzyme denaturation.

Introdução: A Síndrome Metabólica (MS) é uma comorbidade frequentemente encontrada nos pacientes que apresentam Doença Pulmonar Obstrutiva Crônica (DPOC). A DPOC e a MS possuem características em comum e o tabagismo é um fator de risco comum à DPOC e à MS. Apesar da intricada associação entre a DPOC e a MS, sabe-se muito pouco a respeito de como a co-ocorrência da MS afeta a resposta da DPOC ao treinamento físico - um tratamento efetivo para MS e que tem efeito protetor contra o enfisema induzido por tabaco - e à história natural desta. Objetivo: Avaliar como a ingestão crônica de frutose interfere na história natural e nos efeitos do treinamento físico aeróbio sobre a lesão pulmonar induzida por fumaça de cigarro. Métodos: Camundongos C57Bl/6 machos foram divididos em oito grupos (n=16-20/grupo): Controle, Fumo, Exercício, Fumo+Exercício, Frutose, Frutose+Fumo, Frutose+Exercício e Frutose+Fumo+Exercício; e expostos à fumaça de cigarro (30 minutos, 2x/dia), exercício físico (1 hora/dia) ou frutose (20% em água de beber) durante 12 semanas. Após o período de tratamento os animais foram anestesiados, submetidos à avaliação da mecânica respiratória e eutanasiados para coleta de sangue, lavado broncoalveolar (LBA), pulmões e músculos quadríceps para posteriores análises de histologia, dosagem de citocinas e avaliações de expressão gênica e estresse oxidativo. Resultados: A ingestão de frutose causou destruição do septo alveolar comparável com aquela causada pelo fumo (p < 0,001). A combinação de frutose e fumo produziu uma destruição alveolar mais severa do que qualquer um deles sozinho (p=0,008). O exercício físico inibiu o aumento do número total de células inflamatórias e macrófagos no LBA (p < 0,001), impediu o aumento dos níveis de interleucina (IL)-6, IL-10, IL-1beta, TNF-alfa, adiponectina e leptina no plasma e/ou músculo esquelético (p < 0,001), alterou a porcentagem de fibras colágenas e elásticas no parênquima pulmonar (p < 0,001) e atenuou o desenvolvimento do enfisema no grupo Frutose+Fumo+Exercício. Não houve efeito do exercício físico na mecânica respiratória, expressão de genes antioxidantes e estresse oxidativo. Conclusão: O treinamento físico aeróbio atenuou parcialmente o desenvolvimento do enfisema pulmonar em camundongos expostos à fumaça de cigarro e à frutose / Introduction: The Metabolic Syndrome (MS) is a comorbidity frequently presented by patients with Chronic Obstructive Pulmonary Disease (COPD). COPD shares with MS common features and tobacco use is a risk factor for both COPD and MS. Despite of this intricate association between COPD and MS, very little is known about how co-occurrence of MS might affect the response of COPD to physical exercise - an effective treatment for MS that has a protective effect against tobacco-induced COPD - and its natural history. Objective: To evaluate how chronic fructose intake interferes in the natural history and in the effects of aerobic exercise training on lung injury induced by exposure to CS. Methods: Male C57Bl/6 mice were assigned to 8 groups: Control, Smoke, Exercise, Smoke+Exercise, Fructose, Fructose+Smoke, Fructose+Exercise and Fructose+Smoke+Exercise (n=16-20/group) and treated accordingly with CS (30min twice/day), exercise training (1h/day) or fructose (20% in the drinking water) for 12 weeks. After the treatment period the animals were anesthetized, submitted to the evaluation of respiratory mechanics and were euthanized for collect of blood plasma, bronchoalveolar lavage fluid (BALF), lungs and quadriceps muscles for subsequent histology analysis and measures of cytokine levels, gene expression and oxidative stress. Results: Fructose ingestion caused destruction of alveolar septa comparable to that caused by the CS (p < 0,001). Combination of fructose and CS caused an alveolar destruction even more severe than either one alone (p=0,008). Exercise training inhibited the increase of the total number of inflammatory cells and macrophages in BALF (p < 0,001), inhibited the increase of the interleukin (IL)-6, IL-10, IL-1beta, TNF-alpha, adiponectin and leptin levels in plasma and/or skeletal muscle (p < 0,001), altered the percentage of collagen and elastic fibers in lung parenchyma (p < 0,001) and attenuated the development of emphysema in the Fructose+Smoke+Exercise group. There was no effect of exercise training on respiratory mechanics, antioxidant genes expression and oxidative stress. Conclusion: Aerobic exercise training partially attenuated the development of lung emphysema in mice exposed to cigarette smoke and fructose

O remodelamento ósseo é um processo metabólico, dentro do qual os osteoblastos e os osteoclastos, participam ativamente. Portanto, qualquer alteração neste equilíbrio, pode provocar uma modificação na densidade mineral do osso, situação observada em certas doenças osteolíticas como osteoporose, artrite reumatóide e periodontite. Nos últimos anos, há um crescente interesse em avaliar o papel da glicólise na proliferação, sobrevivência e diferenciação dos diferentes tipos celulares. Em particular, tem sido evidenciado o efeito regulador da frutose 1,6-bisfosfato (FBP), um intermediário da via glicolítica de alta energia. Considerando que ainda não existem dados na literatura que correlacionem a FBP com o funcionamento dos osteoclastos, este trabalho tem por finalidade avaliar seu papel na osteoclastogênese e reabsorção óssea in vitro. Para isso, pré-osteoclastos murinos derivados da medula óssea foram diferenciados em osteoclastos na presença de M-CSF, RANKL e duas concentrações da FBP (100 e 300 ?M). Os resultados obtidos amostram que a FBP inibe a diferenciação osteoclástica em uma relação dose-dependente, sem afetar a viabilidade celular. Observa-se também, que o tratamento com FBP diminui a expressão de genes marcadores como, Nfatc1, Trap e Catepsina K (p < 0.01) e das proteínas NFATc1 e catepsina K. Como também, promove uma redução na atividade reabsortiva dos osteoclastos depois de 96 h de cultura. O efeito inibidor da FBP não depende da atividade da piruvato quinase M2 (PKM2). Em conjunto, estes dados sugerem que a FBP é um metabolito regulador importante da osteoclastogênese, demonstrando ser um agente potencial para o tratamento de doenças osteolíticas. / Bone remodeling is a coordinated metabolic process, where the osteoblasts and osteoclasts participate actively. Therefore, any alteration in this balance may cause a change in the bone mineral density, a condition observed in certain bone loss-associated diseases such as osteoporosis, rheumatoid arthritis and periodontitis. Recently, there has been a growing interest in assessing the role of the glycolysis on the proliferation, survival, and differentiation of the different cell types. In particular, it has been demonstrated the protective effect of the Fructose 1,6-bisphosphate (FBP), a high-energy glycolytic intermediate. Considering that there is no evidence in the literature that associate FBP with the function of osteoclasts, this work aims to evaluate its role in osteoclastogenesis and bone resorption in vitro. To this end, murine bone marrow derived pre-osteoclasts were differentiated into osteoclasts in the presence of M-CSF, RANKL and two concentrations of FBP (100 and 300 ?M). The results showed that FBP inhibits the differentiation of osteoclasts in a dose dependent manner, without affecting the cell viability. It was also observed that the treatment with the FBP decreases the expression of marker genes such as Nfatc1, Trap and Cathepsin K (p < 0.01) and the NFATc1 and cathepsin K protein levels. As well, the treatment with FBP resulted in markedly fewer osteoclast activity after 96 h of culture. FBP osteoclast inhibitory effect does not involve Pyruvate Kinase M2 (PKM2) activity. Together, these data denote the important regulatory role of the FBP on osteoclastogenesis, proving to be a potential agent for the treatment of bone loss-associated diseases.