A restrição calórica (RC) é uma intervenção dietética capaz de estender a longevidade de vários organismos. O modelo para RC em Saccharomyces cerevisiae consiste da diminuição da concentração de glicose no meio de cultura e mostra um aumentado tanto do tempo de vida cronológico quanto replicativo. Nosso objetivo foi investigar experimentalmente a ação da RC, focando principalmente nas causas e consequências das modificações de geração de EROs mitocondriais e como estas estão associadas ao processo de envelhecimento. Em um primeiro período de estudos, verificamos quais as fontes mitocondriais de EROs, e comprovamos que uma quantidade significativa se origina de proteínas da matriz mitocondrial, e não da cadeia de transporte de elétrons. Nós estudamos a participação de glicose e de outras fontes de carbono sobre o tempo de vida cronológico em leveduras e mostramos que o aumento da longevidade promovida pela RC está associado à uma mudança de metabolismo fermentativo para respiratório, com participação da via de sinalização de glicose. No estágio realizado no laboratório do Professor Francis Sluse na Université de Liegè, Bélgica, estudamos a ação da RC em leveduras focando nas consequências das modificações no proteoma mitocondrial. Em nosso estudo proteômico, encontramos grandes modificações em proteínas envolvidas com o metabolismo de aminoácidos. Monitoramos a atividade de enzimas relacionadas ao metabolismo de aminoácidos e o tempo de vida cronológico de S. cerevisiae e as mutantes nulas bat2Δ, gdh1Δ, gdh2Δ e gdh3Δ, que codificam a aminotransferase de aminoácidos de cadeia ramificada citosólica, NADP glutamato desidrogenase citosólica, a NAD glutamato desidrogenase mitocondrial, e a NADP glutamato desidrogenase mitocondrial, respectivamente. A atividade da NAD glutamato desidrogenase é aumentada em RC, mas a de NADP glutamato desidrogenase decresce em células controle. Aumentos do tempo de vida cronológico foram observados nas mutantes bat2Δ e gdh1Δ devido a RC, mas nenhuma diferença significativa foi encontrada nas mutantes nulas para Gdh2p e Gdh3p em fase estacionária, indicando que essas proteínas são essenciais para os efeitos benéficos da RC. Nessas células WT crescidas em condições normais e as mutantes nulas apresentam iguais longevidades. Juntos, nossos resultados indicam que o aumento da longevidade em S. cerevisiae promovida pela RC depende da interação entre o sinal de glicose e o metabolismo de aminoácidos. / Calorie restriction (CR) is a dietary intervention capable of extending lifespans in a wide range of organisms. A yeast model of CR has been developed in which limiting the concentration of glucose in growth media of Saccharomyces cerevisiae leads to enhanced chronological and replicative life spans. Our aim was to experimentally investigate the effects of CR, focusing mainly on the causes and consequences of changes in mitochondrial reactive oxygen species (ROS) generation and how these are associated with the aging process. Initially, we looked for sources of mitochondrial ROS, and found that a significant amount of ROS comes from mitochondrial matrix enzymes and not from the electron transport chain. We studied the participation of glucose and other carbon sources in chronological lifespan and show that increased longevity promoted by CR is associated with a metabolism change from fermentation to respiration, with participation of glucose repression pathway. During studies performed in the laboratory of Professor Francis Sluse at the Université de Liège, Belgium, we studied the effect of CR in yeast with focus on the consequences of changes in the mitochondrial proteome. We found large proteomic changes in proteins involved in amino acid metabolism. We monitored the activity of enzymes related to amino acid metabolism and chronological life span of S. cerevisiae null mutants bat2Δ, gdh1Δ, gdh2Δ, and gdh3Δ, which encode for the cytosolic branched-chain amino acid aminotransferase, cytosolic NADP glutamate dehydrogenase, mitochondrial NAD glutamate dehydrogenase and mitochondrial NADP glutamate dehydrogenase, respectively. The activity of NAD glutamate dehydrogenase is increased in CR, but NADP glutamate dehydrogenase decreases in control cells. Increases in chronological life span due to RC were observed in bat2Δ and gdh1Δ mutants, but no significant difference was found in Gdh2p and Gdh3p null mutants in the stationary phase, indicating that these proteins are essential for the beneficial effects of CR. In rich medium, WT cells and null mutants have similar life spans. Together, our results indicate that longevity enhancement by CR in S. cerevisiae depends on the interaction between glucose signals and amino acid metabolism

Made available in DSpace on 2016-04-28T14:16:14Z (GMT). No. of bitstreams: 1 Cesar de Barros Lobato.pdf: 3242160 bytes, checksum: ff8e620459772e7bb401803e69d4f155 (MD5) Previous issue date: 2011-10-11 / Secretaria da Educação do Estado de São Paulo / From a detailed analysis of documents, we realize that historiography does not give due importance to the concepts of caloric and atomic diameter inside the atomic theory developed by John Dalton (1766-1844). In this sense, this thesis aims mainly to show the relevance of these ideas within the Daltonian atomism. We believe they are as important as the atomic weight and need to be better discussed by historiography. Thus, seeking to validate this hypothesis, this work intends to demonstrate two things. The first is to highlight the features that make so special the atomics weights inside the atomic theory, from the point of view Dalton as the point of view of historians. The second is to show that the concept of atomic diameter amalgamated with caloric also have such characteristics and therefore are as important as the idea of atomic weight to Dalton. Through the study, we could see that from the point of view of Dalton, the ideas of atomic weight and diameter are complementary, because one explains the gravimetric results, the other, the results volumetric of the reactions / A partir de uma detalhada análise documental, percebemos que a historiografia não dá a devida importância aos conceitos de calórico e diâmetro atômico, na teoria atômica desenvolvida por John Dalton (1766-1844). Nesse sentido, esta tese tem como objetivo principal, mostrar a relevância desses conceitos dentro do atomismo Daltoniano. Acreditamos que estes são tão importantes quanto o de peso atômico e que precisam ser mais significativamente discutidos pela historiografia. Assim, buscando validar esta hipótese, pretende-se com este trabalho demonstrar duas situações. A primeira é destacar as características que tornam os pesos atômicos tão especiais dentro da teoria atômica, quer seja sob o ponto de vista de Dalton, quanto sob o ponto de vista dos Historiadores. A segunda é mostrar que o conceito de diâmetro atômico amalgamado ao de calórico, igualmente, possui tais características e que por tal razão são tão relevantes quanto à noção de peso atômico para Dalton. Por meio deste estudo, pode-se perceber que sob o ponto de vista de Dalton, as concepções de peso e diâmetro atômico são complementares, pois uma explica os resultados gravimétricos, a outra, os resultados volumétricos das reações

A restrição calórica (RC) estende a expectativa de vida de muitos organismos por mecanismos ainda em estudo. Entre os vários efeitos fisiológicos da RC encontra-se o aumento na biogênese mitocondrial, dependente de óxido nítrico (NO•), sintetizado pela enzima óxido nítrico sintase endotelial (eNOS). Um dos indutores fisiológicos mais potentes da eNOS é a insulina, cujos níveis plasmáticos são consideravelmente reduzidos nos organismos em RC. O objetivo deste trabalho foi investigar os mecanismos associados ao aumento da sinalização por NO• durante a RC in vivo e in vitro, e as conseqüências celulares do aumento de massa mitocondrial no que diz respeito à longevidade e capacidade respiratória celulares. Submetemos camundongos Swiss fêmeas à RC de 40% e observamos um considerável aumento tecido-específico na fosforilação basal de Akt e eNOS em músculo esquelético, tecido adiposo visceral e cérebro, os quais também apresentaram maior massa mitocondrial. A associação entre a sinalização por insulina, NO• e biogênese mitocondrial foi adicionalmente confirmada em um grupo de camundongos tratados com o desacoplador mitocondrial dinitrofenol (DNP), que também reduz a insulinemia e aumenta a longevidade em camundongos. Para o estudo mecanístico deste fenômeno, usamos soros de ratos Sprague-Dawley submetidos à RC de 40% ou alimentados ad libitum (AL) em cultura celular de células vasculares da musculatura lisa (VSMC), reproduzindo um protocolo descrito para RC in vitro. O uso do soro RC aumentou a fosforilação do receptor de insulina e Akt, a expressão de eNOS e nNOS (forma neural da NOS) e a fosforilação de eNOS, o que se refletiu em maior liberação de nitrito (NO2) no meio de cultura. Inibindo-se a Akt, todos os efeitos promovidos pela RC na sinalização por NO• foram revertidos. Ao se imunoprecipitar do soro a adiponectina, citocina conhecida por aumentar a sensibilidade à insulina, aumentada durante a RC, os efeitos do soro RC na via de sinalização de insulina foram abolidos e, conseqüentemente, os efeitos na sinalização por •NO foram prevenidos. Neurônios de células granulosas de cerebelo, que não expressam eNOS, apenas nNOS, foram cultivados com os soros AL ou RC, e também apresentaram considerável aumento na sinalização por •NO. Estas alterações induziram a biogênese mitocondrial e capacidade respiratória, e foram associadas à maior longevidade celular. Os mesmos efeitos mitocondriais foram observados em células secretoras de insulina, INS1, entretanto a secreção de insulina em resposta à glicose tornou-se inibida, por um mecanismo desconhecido, porém associado a reduzidos níveis intracelulares de espécies oxidantes, moléculas-chave para a secreção de insulina; e à alteração da morfologia mitocondrial, provavelmente devido à maior expressão de mitofusina-2 (Mfn-2). Ao se nocautear a Mfn-2, houve um aumento na geração de EROs e as células em RC passaram a secretar insulina a níveis comparáveis aos das células controle. Concluímos que durante a RC a maior sensibilidade à insulina aumenta a atividade de eNOS, via Akt, associada à maior biogênese mitocondrial. A adiponectina é uma molécula-central nestes eventos. A expressão de nNOS também é afetada, por mecanismos desconhecidos. O aumento de biogênese mitocondrial eleva a capacidade respiratória celular e impacta positivamente a longevidade in vitro. A alteração da morfologia mitocondrial associa-se a alterações na produção de oxidantes intracelulares e mudanças na secreção de insulina. / Calorie restriction (RC) is known to extend the lifespan in many organisms, and its mechanisms of action are still under investigation. Enhanced mitochondrial biogenesis driven by nitric oxide (•NO), synthesized by the endothelial nitric oxide synthase (eNOS), is proposed to be a CR central effect. Insulin is one of the most potent physiological activators of eNOS. However, plasmatic insulin levels are dramatically reduced in organisms under CR. The goal of this work was uncover the mechanisms associated with enhanced •NO signaling during CR, in vivo and in vitro, as well as the cellular consequences of increased mitochondrial mass, regarding lifespan and reserve respiratory capability. Female Swiss mice were submitted to 40% of CR. A tissue-specific (skeletal muscle, abdominal adipose tissue and brain) increment in basal Akt and eNOS phosphorylation, which was related to enhanced mitochondrial biogenesis, was observed. Indeed, this association was also verified in tissues from mice treated with low doses of a mitochondrial uncoupler, dinitrophenol (DNP). To unveil the mechanism behind the insulin signaling effects on •NO levels, serum from Sprague-Dawley rats submmited to 40% of CR was used to culture in VSMC cells, an in vitro CR protocol. CR sera enhanced insulin receptor (IR) and Akt phosphorylation, as well as nitrite (NO2-) accumulation in the culture media, the expression of eNOS and nNOS (neural NOS isoform) and eNOS phosphorylation. The effects of CR sera were reversed by Akt inhibition. The immunoprecipitation of serum adiponectin, a cytokine known to improve peripheral insulin sensitivity, also reversed the CR serum effects on insulin and •NO signaling. Cerebellar neurons, which do not express eNOS, just nNOS, were also cultured with CR or AL serum and also presented striking increments in •NO signaling, associated with mitochondrial biogenesis, increased reserve respiratory capability and lifespan extension. The mitochondrial effects promoted by CR were also observed in insulin secreting cells (INS1). However, under the CR condition, insulin secretion stimulated by glucose was impaired. The likely explanations are reduced mitochondrial reactive oxygen species (ROS) generation, or the alteration in mitochondrial morphology, associated, in our model, with enhanced mitofusin-2 expression (Mfn-2). In cells which the Mfn-2 was knocked down, insulin secretion in CR and AL groups was responsive to glucose at the same level, and the intracellular oxidants levels were much higher. Overall, CR improves •NO signaling due to enhanced insulin sensitivity, through Akt, and results in mitochondrial biogenesis. Adiponectin is a key molecule in this phenomenon. Increments in mitochondrial mass enhance the cellular reserve respiratory capability and lifespan. Mitochondrial morphology alterations are associated with possible decreases in ROS generation and impaired insulin release, maintained the low levels of plasmatic insulin.

No description available.

Objective: The objective of the present study was to evaluate the performance of the monothermal caloric screening test in a large sample of patients. Design: A retrospective analysis of the medical records of 1002 consecutive patients who had undergone vestibular assessment at the Mayo Clinic during the years 1989 and 1990 was conducted. Patients with incomplete alternate binaural bithermal (ABB) caloric testing, congenital or periodic alternating nystagmus, or bilateral vestibular loss were excluded from the study. Clinical decision theory analyses (relative operating characteristic curves) were used to determine the accuracy with which the monothermal warm (MWST) and monothermal cool (MCST) caloric screening tests predicted the results of the ABB caloric test. Cumulative distributions were constructed as a function of the cutoff points for monothermal interear difference (IED) to select the cutoff point associated with any combination of true-positive and false-positive rates. Results: Both MWST and MCST performed well above chance level. The test performance for the MWST was significantly better than that of the MCST for three of the four ABB gold standards. A 10% IED cutoff point for the MWST yielded a false-negative rate of either 1% (UW ≥25%) or 3% (UW ≥20%). The use of a 10% IED (UW ≥25%) for the MWST would have resulted in a 40% reduction (N = 294) in the number of ABB caloric tests performed on patients without a unilateral weakness. Conclusions: The results of this study indicated that the MWST decreases test time without sacrificing the sensitivity of the ABB caloric test.

The obesity epidemic continues to be a major concern in the United States. The World Health Organization reported that 1.4 billion adults were either obese or overweight. African American (AA) women have the highest incidence of obesity worldwide. The obesity rate among AAs has continued to rise over the past 2 decades. The problem is that AA women prepare and consume high caloric foods that contribute to obesity. This qualitative descriptive study explored the perceptions that obese AA women have about altering how they prepare soul food to make it a healthier soul food. The empowerment model and the health belief model were used to frame this study. Data were collected using a non-probability purposeful sampling strategy. The sample for this study consisted of 4 focus groups with 6-7 obese AA women (n = 25) who prepare and consume high caloric soul foods and have a body mass index of 30 and above. Focus group transcripts were analyzed using a constant comparative analysis and NVivo 11 computer software. It was found that obese AA women were willing to alter their traditional soul food preparation only if it tastes good. It was also found that participants would maintain new healthier eating behaviors depending on the taste, availability of recipes to use, low cost of healthy ingredients, accessibility of the ingredients, learning how to substitute various herbs and spices, and amount of food waste. Barriers that could limit participation in an intervention designed to develop healthier eating habits were identified as ignorance and laziness, transportation issues, lack of motivation, lack of education, lack of time, no incentives, and bad reviews.

Être capable d’ajuster les quantités consommées selon la densité énergétique des aliments contribue au maintien de l’équilibre de la balance énergétique. Dans un contexte de prévalence du surpoids chez l’enfant, il est crucial d’identifier les facteurs précoces susceptibles d’affecter les capacités d’ajustement énergétique. Durant toute la diversification alimentaire, les quantités ingérées, et donc les capacités d’ajustement énergétique, dépendent en partie de la qualité de l’interaction parent-enfant. Une étude épidémiologique suggère que les capacités d’ajustement énergétique se détérioreraient vers l’âge de un an. C’est aussi à cette période que survient le passage d’une alimentation spécifique bébé à une alimentation de type adulte.Aussi, dans ce travail, nous avons mis en place un suivi longitudinal afin de décrire, à l’aide d’une mesure expérimentale de compensation calorique, les changements développementaux des capacités d’ajustement énergétique entre 11 et 15 mois. Nous avons aussi exploré si certains facteurs relatifs aux caractéristiques individuelles des nourrissons, aux aliments qu’ils avaient consommés ou à l’interaction mère-nourrisson au cours du repas étaient liés aux capacités d’ajustement énergétique.Nous avons mis en évidence qu’à 11 et 15 mois les nourrissons sous-compensent leur prise énergétique à la suite de la consommation d’un premier aliment plus ou moins calorique, avec cependant de grandes différences interindividuelles. L’ajustement énergétique n’est pas meilleur si l’on considère l’ensemble des prises alimentaires au cours des 24h suivant la consommation de ce premier aliment. À 11 mois, les nourrissons ont de meilleures capacités d’ajustement énergétique lorsque, au cours du repas, la mère adapte le rythme des cuillerées à la taille des cuillerées ce qui pourrait refléter un nourrissage réceptif. À 15 mois, les nourrissons ajustent leur prise alimentaire sur des critères volumétriques plutôt que caloriques. Quel que soit l’âge, aucun lien n’a été mis en évidence entre l’expérience alimentaire des nourrissons (lactée et diversifiée) et leurs capacités d’ajustement énergétique. Concernant les changements développementaux, nous avons montré que les capacités d’ajustement énergétique se détériorent de 11 à 15 mois. Les nourrissons pour lesquels cette détérioration est plus importante sont perçus par leur mère comme étant plus ‘attirés’ par la nourriture. De plus, la détérioration des capacités d’ajustement énergétique est associée à une augmentation du z-IMC entre 11 et 15 mois et à un z-IMC plus élevé à 24 mois. Par ailleurs, plus les nourrissons sont exposés à des recettes de légumes de densité énergétique variable entre 8 et 11 mois, moins leur z-IMC est élevé à 8 mois et 11 mois. Ce travail souligne que les capacités d’ajustement énergétique sont associées à différents facteurs précoces relatifs au fonctionnement de la dyade mère-nourrisson et au statut pondéral des nourrissons. Ces résultats ouvrent un nouveau champ de recherche visant à comprendre la causalité de ces liens. In fine, cela permettrait de mieux accompagner les parents pour qu’ils adoptent des pratiques permettant le développement optimal des capacités d’ajustement énergétique de leur enfant au cours de la période clé des 1000 premiers jours. / Being able to adjust food intake according to the energy density of food is one way to self-regulate energy intake and maintain a healthy energy balance. In the context of the prevalence of overweight in children, it appears crucial to identify early factors that may affect caloric adjustment abilities. During the complementary feeding process, the amount consumed, and in turn, the caloric adjustment abilities depend in part on the quality of the caregiver-infant interaction. An epidemiological study suggests that caloric adjustment abilities might deteriorate around one year old; a time when the transition from baby-foods towards adult like foods occurs in the infant diet.In this work, we performed a laboratory-based assessment of the infants’ caloric adjustment ability by adapting the preload paradigm. By using a longitudinal approach, we first described the developmental changes in infants’ caloric adjustment ability between 11 and 15 mo. Then, we explored whether some factors related to the infants’ characteristics, the type of foods consumed or the mother-infant interaction during the meal were linked to the caloric adjustment ability.We showed that, at 11 and 15 mo, the infants under-compensated their energy intake after consuming a food preload more or less caloric. However, we observed large inter-individual variation in this ability. The level of caloric adjustment was not better when considering the total food intake during the 24 h following the food preload consumption. At 11 mo, infants had better caloric adjustment ability when the mother adapted the spoonful pace to the spoonful weight content; this dynamic during the meal could reflect a responsive feeding. At 15 mo, the infants exhibited a volumetric adjustment rather than a caloric adjustment. Regardless of the studied age, no significant links were found between the infants’ feeding experience (milk and complementary foods) and their caloric adjustment ability. Regarding the developmental changes, we observed that the infants’ caloric adjustment ability deteriorated from 11 to 15 mo. The more this deterioration, the more the infants were perceived as ‘attracted by food’ by their mothers. Moreover, the more this deterioration, the more the z-BMI increased between 11 and 15 mo, and the higher the z-BMI was at 24 mo. In addition, the more the infants were exposed to a wide range of energy density for the vegetable-based recipes between 8 and 11 mo, the lower their z-BMI was at 8 and at 11 mo. This work highlights that caloric adjustment ability is associated with various early factors related to the mother-infant dyadic functioning and the infants’ weight status. These results open up a new research field to understand the causality underpinning these links. In fine, this would allow to assist parents to support an optimal development of their infant’s caloric adjustment abilities during the key period of the first 1000 days.

Obesity is a major health problem in the United States and worldwide. It increases the risk for type-2 diabetes and cardiovascular diseases. A chronic low-grade inflammation occurring in white adipose tissue (WAT) is causally linked to the development of insulin resistance (IR), metabolic syndrome and obesity-associated chronic diseases. The aim of this dissertation research was to elucidate the WAT function in metabolic syndrome using genetic (overexpression of an adipose pro-inflammatory hormone, angiotensinogen) and nutritional manipulations/approaches (caloric restriction and omega-3 fatty acids), with specific emphasis on the role of inflammation. Previous research indicates that WAT renin-angiotensin system (RAS) is overactivated in obesity. However, its role in the pathogenesis of IR is hitherto unknown. Using mice overexpressing angiotensinogen (Agt), the only precursor for the hypertensive hormone angiotensin (Ang) II, in WAT, we showed that adipose-specific RAS overactivation leads to systemic IR. This is at least in part due to Ang II, NADPH oxidase and NF-kB-dependent increases in WAT inflammation. Caloric restriction is the main dietary intervention to treat obesity-associated metabolic disorders. While most health agencies recommend a low-fat diet, energy-restricted high-fat diets (HFR) are also claimed to be effective in this regard. Here, we show that weight loss due to HFR is accompanied by improvements of IR but only partial resolution of WAT inflammation. Further, this diet negatively impacted the adipokine profile supporting the current recommendations for low-fat diets. Dietary interventions targeted at reducing WAT inflammation have not been explored in detail. Eicosapentaenoic acid (EPA) is an omega-3 polyunsaturated fatty acid of marine origin with anti-inflammatory properties. We show that EPA is able to both prevent and reverse high-fat diet-induced IR and hepatic steatosis via modulation of WAT inflammation. In conclusion, primary changes occurring in WAT, such as overexpression of Agt, can lead to WAT inflammation and systemic IR. Moreover, nutritional interventions targeting at reducing adiposity (caloric restriction) and inflammation (EPA) can both lead to improvements in systemic IR. Our findings support the current recommendation of low-fat diets for improvement in metabolic profile and show that dietary modulation of WAT function can be used to improve metabolic derangements in obesity.

Purpose: The purpose of this study was to investigate if there was any difference in energy expenditure (kcal/min) and oxygen consumption (VO2) between subjects walking with Masai Barefoot Technology ® (MBT) shoes and regular orthopedic shoes. The research hypothesis was that MBT shoes demand more energy expenditure than regular orthopedic shoes. Methods: Seven women aged 49-65 were recruited for the study. The subjects were tested in two sessions, with a minimum of two weeks in between each sesssion. On each test session the subjects walked with both MBT shoes and orthopedic shoes which were adjusted in mass (g) to match the mass of the MBT shoes. While the subjects walked on a treadmill, the oxygen consumption (VO2), heart rate (min-1) and self selected velocity (m/s) for each of the shoe types was measured. Results: Results showed that there is no significant difference in oxygen consumption (VO2) between the MBT and orthopedic shoes. Energy expenditure (kcal/min) was also calculated from the data and the results revealed that there is no significant differ-ence between MBT and orthopedic shoes in energy expenditure (kcal/min) either. The self selected velocity (m/s) between the two shoe types was also found to be insignificant. Conclusion: The results showed no significant difference between the shoes. This could indicate that the specific construction of the MBT shoe has no effect on the energy expenditure (kcal/min) of its user. This lack of difference may be due to the equal mass of the shoes, but since oxygen consumption (VO2) was not investigated in orthopedic shoes with different shoe masses, this conclusion cannot be confirmed. The self selected velocity (m/s) was found to be insignificant and this finding could suggest to that prolonged usage of the MBT shoe may diminish gait parameters dissimilarities during ambulation. This study should therefore be seen as a pilot study and further investigation in this area should be pursued.

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Resistance training (RT) when associated with the caloric restriction diet (CR) has been shown to have important effects on blood pressure and the aortic artery, minimizing complications due to menopause, such as hypertension. Aim: In this study, we investigated the effects of Ovariectomy and the Resistance Training, Caloric Restriction, and the association of both intervention in systolic blood pressure, matrix metaproteinase-2 activity, aortic vascular reactivity and morphological alterations in ovariectomized Holtzman rats. Material and methods: Fifty female Holtzman rats were subjected to ovariectomy and Sham surgery and distributed into: Sham-sedentary; Ovariectomized-sedentary; Ovariectomized- Resistance Training; Ovariectomized-Caloric Restriction; and Ovariectomized-Resistance Training and Caloric Restriction groups. Resistance Training and 30% Caloric Restriction protocols were performed by 13-weeks. Systolic blood pressure, acetylcholine, and sodium nitroprusside induced relaxation of aortic rings; the hematoxylin-eosin stain used to highlight the aortas wall cross-sectional area and the matrix metaproteinase-2 activity, insulin tolerance test and aorta vessel remodeling were analyzed. Results: We observed that, Ovariectomy increased systolic blood pressure, decreased potency in dependent and independent endothelium relaxation and matrix metaproteinase-2 activity, promoted insulin resistance and aorta vessel remodeling in cross-sectional area, media to lumen ratio, collagen content and alter structure and elastic fibers of the vessel. However, the association of exercise and diet prevent the increase systolic blood pressure, improved the relaxation potency in dependent and independent endothelium relaxation, elevated the matrix metaproteinase-2 activity, increased the aorta cross-sectional area, media to lumen ratio, decreased collagen content and alter elastic fibers in aorta vessel wall. Conclusion: Our study reveled that the association of resistance training and caloric restriction can prevent the hypertensive condition, improve vascular function, activate matrix metaproteinase-2, and produce a beneficial hypertrophic remodeling with increased vascular compliance in ovariectomy in Holtzman rats. / Introdução: A hipertensão é um importante fator de risco para doenças cardiovasculares na menopausa. O treinamento resistido (TR) quando associado à dieta de restrição calórica (RC) têm demonstrado importantes efeitos sobre a pressão arterial e a artéria aorta, minimizando complicações decorrentes da menopausa, como a hipertensão arterial. Objetivo: O presente trabalho tem como objetivo investigar os efeitos da ovariectomia e das intervenções de TR, RC e da associação de ambos (TR+RC) sobre a pressão arterial sistólica, reatividade vascular aórtica, resposta insulínica, atividade da metaloproteinase de matriz 2 e alterações morfológicas em ratas Holtzman. Materiais e métodos: Cinquenta ratas Holtzman foram submetidas à cirurgia de ovariectomia e Sham; e distribuídas nos seguintes grupos (n=10): Sham-sedentária, Ovariectomizada-sedentária, treinamento resistido ovariectomizada, restrição calórica ovariectomizada e treinamento resistido associada à restrição calórica ovariectomizada. Os protocolos de TR e 30% de RC foram realizados por 13 semanas. A pressão arterial sistólica, teste de tolerância à insulina, reatividade vascular em anéis aórticos, atividade da metaloproteinase de matriz 2, análises morfológicas utilizando coloração de Hematoxilina e Eosina, Tricrômio de Masson e Pricrosírius-red foram realizadas. Resultados: Observamos que a ovariectomia aumentou a pressão arterial sistólica, promoveu resistência à insulina, diminuiu a potência do relaxamento dependente e independente do endotélio e atividade da metaloproteinase de matriz 2, além de promover o remodelamento do vaso aórtico sobre a área da secção transversal, relação túnica média/lúmen, alterando o conteúdo de colágeno e fibras elásticas da artéria aorta. No entanto, a associação entre exercício e dieta e ambos separados, preveniram o aumento da pressão arterial sistólica, melhoraram a potência do relaxamento dependente e independente do endotélio, promoveram ativação da metaloproteinase de matriz 2, aumento da área da secção transversal da aorta, da relação túnica média/lúmen, além de promover a diminuição do conteúdo de colágeno e alteração das fibras elásticas na parede do vaso aórtico. Conclusão: O presente estudo mostrou que os efeitos do TR e RC, associados ou realizados separadamente, foram eficientes para melhorar os parâmetros clínicos e moleculares, prevenindo o surgimento da condição de hipertensão, melhorando a função vascular, a resposta insulínica, a atividade da metaloproteinase de matriz 2 e o remodelamento da aorta com aumento da complacência vascular, na condição de hipertensão induzida pela ovariectomia em ratas Holtzman. / FAPESP: 2012/21087-4