Thesis (Ph.D.)--Aberdeen University, 2008. / Includes bibliographical references.

The principal aim of this thesis was to investigate the effects of altering the energy density of the diet (kJ/g) on post-restriction weight regain in domestic cats and laboratory mice. Secondly, evidence for body weight regulation was examined in mice. In cats, consumption of the same number of calories of a low energy dense diet (with added water) induced significantly less weight rebound than a more energy dense diet (with no added water). This was accounted for by differences in physical activity, as cats on the low energy dense diet were significantly more active. It was assumed the less energy dense diet held cats in a perceived state of energy restriction and they were actively searching for more food. In mice, cellulose was used to alter the energy density of the diet. Post-restriction body weight rebound was also observed on an energy dense diet (no cellulose). However, body weight not did reach pre-restriction levels when consuming a low energy dense diet (with added cellulose) and digestibility was significantly reduced. It was likely that the fibre-rich induced a gut processing limit on the bulk of digestible food that could be consumed. Overall, the energy density of the diet was shown to modulate post-restriction body weight rebound, but results varied with species and the energy dilutant used. The implications for human weight management have yet to be elucidated. The second principle finding was that post-restriction hyperphagia was induced to replenish food deficiencies incurred during caloric restriction, rather than to replenish body mass loss in mice. This provided preliminary evidence for a ‘calorie-counting’ body weight regulatory system in mammals.

Nicotine, the major psychoactive ingredient of tobacco smoke, underlies numerous effects by activating neuronal nicotinic acetylcholine receptors. Both in vitro and in vivo studies suggest that nicotine is neuroprotective and improves cognitive performance. Epidemiology studies show that smoking is negatively correlated with the incidence of Parkinson's disease and Alzheimer's disease. Postmortem research and neuroimaging studies show that loss of nicotinic binding sites in the brain is the major feature of neurodegenerative diseases related to dementia and cognitive impairment. Caloric restriction, a regimen that extends the lifespan in all mammalian species studied so far including rodents and primates, is a highly regulated response to food deprivation. It is believed that the longevity effect of caloric restriction is mediated by SIRT1, a NAD-dependent deacetylase, and its related genes. Nicotine's effect on body weight could also lead to weight loss by decreasing caloric absorption consumption. The goal of this study was to find the possible correlation between nicotine's effects and the activation of SIRT1 and its related genes. Using beta2-/- mice that lack high affinity beta2 nicotinic acetylcholine receptors (nAChRs), we first demonstrated that beta2* nAChRs do not directly regulate expression of survival genes. However, we found that loss of beta2* nAChRs could result in augmented cellular stress, which indirectly increased expression of SIRT1, Nampt, and Ku70, possibly as an adaptive response to provide protection against neurodegeneration. We also found that loss of endogenous activation of beta2* nAChRs had less effect on synaptic connections but strongly impaired survival of hippocampal GABAergic neurons. To activate beta2* nAChRs in normal mice, we administered nicotine through drinking water. In a short-term exposure study, we determined the dose of nicotine to be used in young adult mice, and found that chronic nicotine treatment was anxiolytic, decreased caloric consumption, increased nAChR binding sites, and most importantly, increased expression of SIRT1 and its related genes. Finally, we compared long-term nicotine treatment with caloric restriction in middle-aged mice to examine their effects to brain aging, and our results indicated that in mice long term caloric restriction and nicotine treatment both tend to improve memory in aging mice, but appear to act through different mechanisms.

Orientador: Patrícia Aline Boer / Banca: Carlos Alan Candido Dias Junior / Banca: Patricia Simone Leite Vilamaior / Resumo: Introdução. Estudos anteriores mostram que a restrição proteica gestacional é responsável pela redução do número de néfrons e hipertensão arterial. O aumento da pressão arterial leva a uma hiperfiltração glomerular e consequentemente ruptura da barreira de filtração, com início do quadro de glomeruloesclerose. Além disso, evidências destacam as consequências da dieta hiperlipídica sobre a morfologia e distúrbios funcionais renais. O presente estudo tem como objetivo avaliar o efeito da sobrecarga calórica por dieta hiperlipídica sobre a função e morfologia renal em ratos submetidos à restrição proteica gestacional. Método. Após confirmação da prenhez as ratas foram divididos em 2 grupos, sendo grupo NP (normal protein - 17% de caseína na gestação) e grupo LP (low protein - 6% de caseína durante a gestação). Após nascimento a prole de ratos machos foi mantida com ração normal, sendo que da 8ª até a 13ª semana de vida essa prole foi submetida à dieta hiperlipídica (grupos LPH e NPH) ou ração padrão para roedores (grupo LPN e NPN). Foram realizadas análises da função renal, aferição da pressão arterial, imunohistoquímica, microscopia eletrônica de varredura e análise bioquímica do perfil lipídico. Resultados. O índice de adiposidade estava reduzido em LPN e aumentado nos grupos NPH e LPH. Observamos aumento da concentração de colesterol total em NPH e LPH, e aumento de colesterol LDL em LPH. A pressão arterial estava significativamente aumentada nos animais do grupo LPH na 10ª e 12ª semana de vida, comparado aos outros grupos no mesmo período. A menor excreção urinária de sódio foi observada nos grupos tratados, enquanto os animais NPH e LPN apresentaram aumento da acidificação urinária de forma tempo-dependente da dieta hiperlipídica. Os grupos LPN, NPH e LPH mostraram um aumento da expressão de AT1r, fator de transformação do crescimento beta (TGFβ-1), colágeno ... / Abstract: Background. Prior studies show that maternal protein-restricted offspring (LP) have pronounced reduction of nephron number and arterial hypertension associated with unchanged glomerular filtration rate and enhanced glomerular area that may be related with glomerular hyperfiltration/overflow and account for the glomerular filtration barrier breakdown and early glomerulosclerosis. Additionally, evidence is emerging that highlights the far-reaching consequences of high fat diet (HFD) on kidney morphology and function disorders. The present study aims to evaluate the effect of HFD on renal function and morphology in LP rats. Methods. Maternal protein-restricted offspring (LP, 6% casein) and normal protein intake rats (NP, 17% casein) were submitted to ingestion of HFD (LPH and NPH, respectively) or standard chow to rodents (LPN and NPN) from 8th to 13th of age. Renal Function, systemic arterial pressure, immunohistochemistry and scanning electron microscopy were performed and biochemical serum parameters analyzed. Results. The body adiposity and mass were reduced in LPN which in turn, increased in NPH and LPH groups. Striking increased in total cholesterol was observed in NPH and LPH, and increased LDL in LPH. The blood pressure was significant increase in LPH groups from the 10th and 12th week of life compared to the other groups. A reduced urinary excretion of sodium was observed in low-protein treated rats while NPH and LPH animals presented an increased urinary acidification in time-dependent fashion. The LPN, NPH and LPH groups showed an increased expression of AT1r, transforming growth factor (TGFβ-1), collagen and fibronectin. By ultraestructural analysis we found a pronounced enfacement of foot process in treated groups and HFD-treated offspring showed wear-out of podocytes by rupture of cell membranes. In parallel all treated rats present a significant urinary protein excretion. Conclusion. In conclusion, from our present ... / Mestre

Made available in DSpace on 2014-11-10T11:09:39Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-02-25Bitstream added on 2014-11-10T11:58:06Z : No. of bitstreams: 1 000789732.pdf: 2864828 bytes, checksum: 411b76b95ee202f65447d9e42d3b9889 (MD5) / Introdução. Estudos anteriores mostram que a restrição proteica gestacional é responsável pela redução do número de néfrons e hipertensão arterial. O aumento da pressão arterial leva a uma hiperfiltração glomerular e consequentemente ruptura da barreira de filtração, com início do quadro de glomeruloesclerose. Além disso, evidências destacam as consequências da dieta hiperlipídica sobre a morfologia e distúrbios funcionais renais. O presente estudo tem como objetivo avaliar o efeito da sobrecarga calórica por dieta hiperlipídica sobre a função e morfologia renal em ratos submetidos à restrição proteica gestacional. Método. Após confirmação da prenhez as ratas foram divididos em 2 grupos, sendo grupo NP (normal protein - 17% de caseína na gestação) e grupo LP (low protein - 6% de caseína durante a gestação). Após nascimento a prole de ratos machos foi mantida com ração normal, sendo que da 8ª até a 13ª semana de vida essa prole foi submetida à dieta hiperlipídica (grupos LPH e NPH) ou ração padrão para roedores (grupo LPN e NPN). Foram realizadas análises da função renal, aferição da pressão arterial, imunohistoquímica, microscopia eletrônica de varredura e análise bioquímica do perfil lipídico. Resultados. O índice de adiposidade estava reduzido em LPN e aumentado nos grupos NPH e LPH. Observamos aumento da concentração de colesterol total em NPH e LPH, e aumento de colesterol LDL em LPH. A pressão arterial estava significativamente aumentada nos animais do grupo LPH na 10ª e 12ª semana de vida, comparado aos outros grupos no mesmo período. A menor excreção urinária de sódio foi observada nos grupos tratados, enquanto os animais NPH e LPN apresentaram aumento da acidificação urinária de forma tempo-dependente da dieta hiperlipídica. Os grupos LPN, NPH e LPH mostraram um aumento da expressão de AT1r, fator de transformação do crescimento beta (TGFβ-1), colágeno ... / Background. Prior studies show that maternal protein-restricted offspring (LP) have pronounced reduction of nephron number and arterial hypertension associated with unchanged glomerular filtration rate and enhanced glomerular area that may be related with glomerular hyperfiltration/overflow and account for the glomerular filtration barrier breakdown and early glomerulosclerosis. Additionally, evidence is emerging that highlights the far-reaching consequences of high fat diet (HFD) on kidney morphology and function disorders. The present study aims to evaluate the effect of HFD on renal function and morphology in LP rats. Methods. Maternal protein-restricted offspring (LP, 6% casein) and normal protein intake rats (NP, 17% casein) were submitted to ingestion of HFD (LPH and NPH, respectively) or standard chow to rodents (LPN and NPN) from 8th to 13th of age. Renal Function, systemic arterial pressure, immunohistochemistry and scanning electron microscopy were performed and biochemical serum parameters analyzed. Results. The body adiposity and mass were reduced in LPN which in turn, increased in NPH and LPH groups. Striking increased in total cholesterol was observed in NPH and LPH, and increased LDL in LPH. The blood pressure was significant increase in LPH groups from the 10th and 12th week of life compared to the other groups. A reduced urinary excretion of sodium was observed in low-protein treated rats while NPH and LPH animals presented an increased urinary acidification in time-dependent fashion. The LPN, NPH and LPH groups showed an increased expression of AT1r, transforming growth factor (TGFβ-1), collagen and fibronectin. By ultraestructural analysis we found a pronounced enfacement of foot process in treated groups and HFD-treated offspring showed wear-out of podocytes by rupture of cell membranes. In parallel all treated rats present a significant urinary protein excretion. Conclusion. In conclusion, from our present ...

Les études à long-terme confirment que la combinaison d’un déficit calorique et d’un programme d’exercice est une intervention plus profitable quant à la perte de poids qu’un régime hypocalorique ou un programme d’exercice seul. Toutefois, la perte de poids moyenne de l’approche combinée est en générale inférieure à celle estimée sur la base du déficit calorique et de la dépense énergétique du programme d’exercice. L’objectif principal de cette étude portait sur l’investigation des effets d’un déficit calorique et de l’exercice sur l’apport calorique, la dépense énergétique totale, la thermogenèse d’origine autre que l’exercice et la compensation alimentaire post-exercice chez les jeunes femmes. Huit jeunes femmes de poids normal et inactives ont participé à quatre conditions expérimentales : contrôle; exercice, où une séance d’exercice à intensité modérée a été réalisée; déficit calorique, où un déficit calorique de 25% pour une période de 3 jours consécutifs a été respecté; et exercice/déficit calorique. À la suite de chaque session, un repas ad libitum à l’heure du dîner a été offert aux participantes et des boîtes à lunch contenant des aliments à volonté choisis par l’entremise de menu ont été remises à ces dernières pour couvrir l’apport calorique pour la journée (jour 1) ainsi que la journée subséquente (jour 2). De plus, un accéléromètre a été remis à chaque participante après chaque séance expérimentale pour être en mesure d’estimer la dépense énergétique liée à l’activité physique pour le jour 1 et jour 2. Aucune différence significative n’a été observée entre les différentes conditions expérimentales pour l’apport calorique au repas ad libitum post-exercice, au jour 1 ainsi qu’au jour 2. De plus, aucune différence significative n’a été notée pour la dépense énergétique totale ainsi que la thermogenèse d’origine autre que l’exercice et aucune compensation alimentaire post-exercice n’a été observée en fonction des conditions expérimentales. Ces résultats suggèrent que la combinaison d’un déficit calorique de 3 journées consécutives avant une séance d’exercice d’intensité modérée n’influence pas l’apport calorique post-exercice, la dépense énergétique totale, la thermogenèse d’origine autre que l’exercice et n’engendre pas de compensation alimentaire post-exercice. Un déficit calorique combiné à l’exercice d’une période plus prolongée pourrait être nécessaire afin d’observer une augmentation de la compensation alimentaire post-exercice pendant une intervention qui vise à induire une perte de poids.

L'autophagie est un processus d'auto-digestion durant lequel les cellule dégradent leurs propres composants afin de maintenir l’homéostasie en conditions basales. L'autophagie est donc nécessaire à l’échelle de la cellule et de l’organisme car elle joue un rôle dans l’élimination des organites endommagés et des agrégats de protéines potentiellement nocifs et a la capacité de mobiliser les métabolites essentiels des réserves énergétiques en conditions de stressLa détérioration des fonctions cellulaires et au niveau de l’organisme liée à l'âge est associée à une dérégulation des voies de détection des nutriments ainsi qu’à une autophagie déficiente. La réactivation du flux autophagique peut prévenir ou améliorer ces dysfonctionnements métaboliques liés à l'âge. Les composés non toxiques capables de réduire les taux globaux d'acétylation des protéines et d'induire l'autophagie ont été classés dans la catégorie des agents mimétiques de restriction calorique (CRMs, de l’anglais « caloric restriction mimetic »). Nous montrons ici que l'aspirine et son métabolite actif, le salicylate, induisent une autophagie en raison de leur capacité à inhiber l'activité acétyltransférase de EP300. Alors que le salicylate stimule le flux autophagique dans les cellules « Wild Type », il ne permet pas d’augmenter le niveau d'autophagie dans les cellules déficientes en EP300, ni dans les cellules dans lesquelles EP300 endogène a été remplacé par les mutants EP300 résistants au salicylate. En conséquence, l'activité pro-autophagique de l'aspirine et du salicylate sur le nématode Caenorhabditis elegans est perdue lorsque l'expression de l'orthologue EP300 cpb-1 est réduite. Ces résultats permettent de conclure que l'aspirine est un CRM dont le mécanisme est conservé au cours de l’évolution. / Autophagy is a self-digestion process in which cell degrades its own components in order to maintain homeostasis in basal conditions; autophagy is required for the maintenance of cellular and organismal fitness due to its role in eliminating damaged organelles and potentially harmful protein aggregates, as well as its unique capacity to mobilize essential metabolites from complex energy stores in conditions of stress.The age-associated deterioration in cellular and organismal functions associates with dysregulation of nutrient-sensing pathways and disabled autophagy. The reactivation of autophagic flux may prevent or ameliorate age-related metabolic dysfunctions. Non-toxic compounds endowed with the capacity to reduce the overall levels of protein acetylation and to induce autophagy have been categorized as caloric restriction mimetics (CRMs). Here, we show that aspirin or its active metabolite salicylate induce autophagy by virtue of their capacity to inhibit the acetyltransferase activity of EP300. While salicylate readily stimulates autophagic flux in control cells, it fails to further increase autophagy levels in EP300-deficient cells, as well as in cells in which endogenous EP300 has been replaced by salicylate-resistant EP300 mutants. Accordingly, the pro-autophagic activity of aspirin and salicylate on the nematode Caenorhabditis elegans is lost when the expression of the EP300 ortholog cpb-1 is reduced. Altogether, these findings identify aspirin as an evolutionary conserved CRM.

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INTRODUÇÃO: O treinamento físico promove ao indivíduo benefícios morfológicos, fisiológicos e funcionais. Contudo, o afastamento temporário ou permanente da rotina de treinamento (destreinamento físico), pode resultar em rápido aumento de peso, dislipidemia, inflamação e resistência à insulina. Em contrapartida, a restrição calórica é uma alternativa nutricional utilizada para perder peso e tem sido associada à ativação de vias envolvidas no metabolismo lipídico, sensibilidade à insulina e inflamação. Além disso, a suplementação com aminoácidos de cadeia ramificada é uma prática comum entre atletas e dentre eles, a leucina demonstra estimular a síntese proteica, a oxidação de ácidos graxos e o metabolismo da glicose. Visto isso, sugere-se que a associação dessas duas intervenções nutricionais possa atenuar os danos no fígado decorrentes do destreinamento físico. OBJETIVOS: Verificar se a restrição calórica de 30% associada ou não à suplementação com 5% de leucina atenua as alterações no perfil lipídico, na inflamação e na via de sinalização da insulina no fígado de animais submetidos ao destreinamento físico. MÉTODOS: Foram utilizados 64 ratos Sprague-Dawley, machos e adultos. Os animais foram distribuídos em grupo controle (CON; n=16) e treinado (TR; n=48). Em seguida, os animais do grupo TR foram redistribuídos em 5 grupos: TR (n=16); Destreinamento (DT; n=8); DT + Suplementação com leucina (LEU; n=8); Grupo DT + Restrição Calórica (RC; n=8); Grupo DT+ RC + LEU (LEU+RC; n=8). A eutanásia ocorreu no final da 14ª semana e foram analisados: consumo de ração, peso corporal, composição corporal, sensibilidade à insulina, tolerância à glicose, concentração de triglicerídeos e colesterol no fígado, adipocinas no soro (adiponectina, leptina, IL-6, IL-10) e no fígado (IL-6, IL-10 e TNF-&#945;). Também foram mensurados no fígado parâmetros moleculares, incluindo a atividade de ligação do NF-kB, e expressão das proteinas SIRT-1, pAMPKThr172, AKT total, pAKT308 e FoxO1; e os genes PEPCK, PPAR-&#945;, SREBP-1c, FAS e ACC. ESTATÍSTICA: A normalidade foi previamente analisada pelo teste Shapiro-Wilk. As variáveis nas quais a normalidade não foi confirmada, procedimentos não paramétricos foram utilizados. Os dados foram expressos em média e desvio padrão e o Teste T de Student foi utilizado para amostras independentes. As comparações entre os grupos foram avaliadas por meio de análise de variância (ANOVA), seguida do teste de Tukey, para identificação dos contrastes significantes. Para todas as análises foi considerado um nível de significância de 5%. A análise estatística foi realizada no software GraphPad Prism versão 5.0. RESULTADOS: Os grupos RC e LEU+RC apresentaram peso corporal (p<0,05) e % de gordura da carcaça (p<0,05) significativamente menores do que os grupos DT e LEU. O grupo DT apresentou maior peso relativo do tecido adiposo em relação aos grupos RC e LEU+RC (p<0,05). A insulina sérica e o teste te tolerância à insulina não apresentaram diferença significativa. Na 13ª semana os grupos RC e LEU+RC apresentaram tolerância à glicose significativamente menor do que grupo DT (p<0,05). O grupo DT apresentou aumento significativo na tolerância à glicose entre a 8ª e 13ª semana (p<0,05). A leptina sérica foi significativamente maior no grupo DT em relação ao grupo RC e LEU+RC (p=0,0002), e a adiponectina sérica e a razão adiponectina/leptina não exibiu diferença significativa entre os grupos. O grupo LEU+RC apresentou concentraçao significativamente maior de IL-6 no soro relação o grupo LEU (p=0,0064), contudo houve diferença significativa na concentração de IL-10 ou na razão IL6/IL-10. A razão IL-6/IL-10 (p=0,0214) no fígado foi significativamente maior no grupo LEU em relação ao grupo LEU+RC. A razão TNF- &#945;/IL-10 foi significativamente maior no grupo DT em comparação ao grupo LEU (p=0,0094). A IL-6 apresentou correlação positiva com peso relativo do tecido adiposo enquanto a IL-10 apresentou correlação negativa. A atividade de ligação do NF-kB não apresentou diferença significativa. A concentração de triglicerídeos no fígado foi significativamente maior no grupo LEU do que no grupo LEU+RC (p=0,0127). A concentração de colesterol foi significativamente maior no grupo DT em comparação ao grupo RC (p=0,0115). Nos parâmetros moleculares a expressão da SIRT-1 foi significativamente maior nos grupos RC e LEU+RC em comparação ao grupo DT (p<0,0005) e a expressão das demais proteínas não exibiram diferença significativa. O grupo LEU+RC apresentou a expressão significativamente maior dos genes PPAR-&#945; (p=0,0034), ACC (p=0,0003), FAS (p<0,0001) e SREBP-1c (p=0,0032) em relação ao grupo DT. O grupo RC apresentou expressão significativamente maior do gene SREBP-1c (p=0,0032) em relação ao grupo DT. CONCLUSÃO: A restrição calórica amenizou a concentração de colesterol no fígado e quando associada a suplementação com leucina reduziu a síntese de triglicerídeos nesse órgão. A razão adiponectina/leptina e o teste de OGTT indicaram melhor sensibilidade à insulina e tolerância à glicose nos grupos submetidos à restrição calórica associada ou não à suplementação com leucina. A expressão dos genes SREBP-1c e PPAR- &#945; e da proteína SIRT-1 demonstraram ser um indicativo de melhor sensibilidade à insulina hepática. / INTRODUCTION: The physical training promotes the individual morphological, physiological and functional benefits. However, the temporary or permanent departure from the training routine (physical detraining), can result in fast weight gain, dyslipidemia, inflammation and insulin resistance. On the other hand, the caloric restriction is a nutricional alternative to lose weight and have been associated with activation pathways involved in lipid metabolism, insulin sensitivity and inflammation. Besides that, branched-chain amino acid supplementation is a common practice between athletes and among them, the leucine shows stimulate protein synthesis, fatty acid oxidation and glucose metabolism. Based on that, it is suggested that the association of these two nutritional interventions can attenuate liver damage resultant from physical detraining. OBJECTIVES: Check if a caloric restriction of 30% associates or not of 5% leucine supplementation attenuates the changes in the lipid profile, inflammation and insulin signaling pathway in the liver of animals subjected to physical detraining. METHODS: It were used 64 rats Sprague-Dawley, males and adults. The animals were distributed in control group (CON; n=16) and trained (TR; n=48). Then, control group animals were redistributed in 5 groups: TR (n=16); Detraining (DT; n=8); DT + Supplementation with leucine (LEU; n=8); Group DT + Caloric Restriction (CR; n=8); Group DT+ CR + LEU (LEU+CR; n=8). The euthanasia occurred at the end of the 14th week and were anlyzed: feed intake, body weight, body composition, insulin sensitivity, glucose tolerance, triglyceride and cholesterol concentration in the liver, adipokines in serum (adiponectin , leptin, IL-6 , IL-10) and liver (IL-6, IL-10). Also were measured in the liver molecular parameters, including binding activity from NF-kB, and protein expression SIRT-1, pAMPKThr172, AKT total, pAKT308 and FoxO1; and the genes PEPCK, PPAR-&#945;, SREBP-1c, FAS and ACC. STATISTICS: The normality was previously analyzed by Shapiro-Wilk test. The variables where normality wasn\'t confirmed, non-parametric procedures were used. The data were expressed as mean and standard error and Student\'s t-test was used for independent samples. The comparisons between groups were evaluated using analysis of variance (ANOVA), followed by the Tukey test to identify significant contrasts. For all analyzes was considered 5% significance level. The statistical analysis was performed on software GraphPad Prism version 5.0. RESULTS: The CR and LEU+CR groups showed body weight (p<0,05) and % carcass fat (p<0,05) significantly lower than DT and LEU groups. The DT group showed higher relative weight of adipose tissue in relation to RC and LEU+CR groups (p<0,05). In the serum insulin and insulin tolerance test there were no significant differences. At 13th week the RC and LEU+CR groups showed glucose tolerance significantly lower than DT group (p<0,05). The DT group showed significant increase in glucose tolerance between the 8th and 13th week (p<0,05). The serum leptin was significantly higher in DT group compared to the CR and LEU + CR group (p=0,0002), and the serum adiponectin and the reason adiponectin/leptin showed no significant difference between groups. The LEU+CR group showed significantly higher serum IL-6 concentration compared with the LEU group (p=0,0064), however there was a significant difference in IL-10 concentration or reason IL-6/IL-10. This reason in the liver was significantly higher in LEU group compared to the LEU+CR group. The IL-6 showed positive correlation with relative weight of the adipose tissue while the IL-10 showed negative correlation. The binding activity of NF-kB showed no significant difference. The concentration of triglycerides in the liver was significantly higher in LEU group compared to LEU+CR group (p=0,0127). The concentration of cholesterol was significantly higher in DT group compared to the RC group (p=0,0115). In the molecular parameters the SIRT-1 expression was significantly higher in CR and LEU+CR group compared to the DT group (p<0,0005) and the other protein expression there was no significant difference. The LEU+CR group showed the expression significantly higher of the genes PPAR-&#945; (p=0,0034), ACC (p=0,0003), FAS (p<0,0001) and SREBP-1c (p=0,0032) compared to the DT group. The CR group showed expression significantly higher of the gene SREBP-1c (p=0,0032) compared of the DT group. CONCLUSION: The caloric restriction softened the concentration of cholesterol in the liver and when combined with a leucine supplementation decreased triglyceride synthesis in this organ. The reason adiponectin/leptin and the OGTT test indicated better insulin sensitivity and glucose tolerance in groups submited calorie restriction with or without leucine supplementation. The expression of SREBP-1c and PPAR-&#945; genes and SIRT-1 protein showed to be indicative of better hepatic insulin sensitivity.

Diversos estudos demonstram que os benefícios induzidos pelo exercício físico são revertidos após a interrupção do mesmo. Essa interrupção, também conhecida como destreinamento físico, leva ao aumento da massa corporal, ganho de massa adiposa e resistência à insulina. Apesar dessas evidências, pouca atenção é destinada para investigação de estratégias que possam atenuar esse quadro. Portanto, o objetivo deste trabalho foi investigar os efeitos da restrição calórica sobre sensibilidade à insulina e os marcadores de inflamação no tecido adiposo epididimal de ratos destreinados. A amostra foi composta por 32 ratos Sprague-Dawley, machos e adultos. Inicialmente, os animais foram distribuídos em 2 grupos: Controle (CON) e Treinamento (TREIN), animais que foram submetidos ao treinamento em esteira ergométrica durante 8 semanas. Em seguida os animais TREIN foram redistribuídos em três grupos: Um grupo foi constituído por animais que continuaram o programa de treinamento físico (TF) por 6 semanas e mantidos ao acesso de ração ad libitum (TREIN). Os outros dois grupos tiveram o TF interrompido e foram mantidos ao acesso de ração ad libitum (DT) ou a restrição calórica de 30% (DTRC) por 6 semanas. Os animais do grupo CON continuaram o experimento, por mais 6 semanas, sem realizar qualquer tipo de exercício físico. A mensuração da massa corporal e o teste oral de tolerância à glicose foram realizados na oitava e na décima terceira semana de experimento. A partir disso, foi calculado o delta percentual da massa corporal (&#916;%MC) e da área sob a curva glicêmica (&#916;%ASC). Após 14 semanas de experimento, os animais foram eutanasiados para determinação da composição corporal. Também, foram analisadas proteínas envolvidas na via de sinalização da insulina (PKB), proteínas e adipocinas envolvidas no proceso inflamatório (PKC; IKK-beta; JNK; TNF-&#945;; leptina; adiponectina)O grupo DTRC apresentou valores significativamente menores para &#916;%MC ,&#916;%ASC e gordura relativa comparado ao DT Além disso, os valores encontrados no grupo DT foram estatisticamente maiores em comparação ao TREIN. Por outro lado, a massa livre de gordura relativa foi estatisticamente menor no grupo DT em contraste aos grupos DTRC e TREIN. Baseados nesses resultados, conclui-se que a restrição calórica foi capaz de atenuar o ganho de peso corporal e massa adiposa, além de evitar a diminuição da sensibilidade à insulina e da massa livre de gordura após 6 semanas de destreinamento físico. / Several studies show that the benefits induced by exercise are reversed after cessation it. This interrupt, also known as physical detraining leads to increased body weight, body mass gain and insulin resistance. Despite this evidence, little attention is directed to investigate strategies to increase this situation. Therefore, the aim of this study was to investigate the effects of calorie restriction on insulin sensitivity and inflammation markers in epididymal adipose tissue of rats untrained. The sample consisted of 32 male Sprague-Dawley male and adult. Initially, the animals were divided into 2 groups: control (CON) and Training (TREIN), animals underwent training on a treadmill for 8 weeks. Then TREIN animals were divided in three groups: One group was composed of animals that continued the program of physical training (PT) for 6 weeks and maintained access to food ad libitum (TREIN). The other two groups had stopped and the TF were maintained ad libitum access to food (TD) or 30% caloric restriction (DTRC) for 6 weeks. The animals in the CON group continued the experiment for another 6 weeks, without performing any type of exercise. The measurement of body mass test and oral glucose tolerance were carried out in the eighth and the thirteenth week of the experiment. From this, we calculated the percentage of body mass delta (&#916;% MC) and the area under the glucose curve (&#916;% AUC). After 14 weeks, the animals were euthanized for determination of body composition. Also, we analyzed the proteins involved in insulin signaling pathway (PKB) and protein adipokines involved in inflammatory pathway (PKC; IKK-beta; JNK, TNF-&#945;, leptin, adiponectin) DTRC group showed significantly lower values for &#916;% MC, &#916;% AUC and fat on the TD compared Furthermore, the values DT group were significantly higher compared to TREIN. Moreover, the relative fat-free mass was lower in the DT group in contrast to groups and DTRC TREIN. Based on these results, it is concluded that caloric restriction was able to attenuate the gain in body weight and fat mass, in addition to preventing the decrease in insulin sensitivity and fat free mass after 6 weeks detraining physical.