Orientador: Ana Angélica Henrique Fernandes / Banca: Antonio Francisco Godinho / Banca: Haydeé Maria Moreira / Resumo: Sedentarismo e hábitos alimentares inadequados, tais como, dietas restritivas e hipercalóricas são fatores relevantes a serem considerados. Este estilo de vida contemporâneo, que restringe o tempo gasto com alimentação e inatividade física, principalmente aqueles relacionados às alterações cardiovasculares. Para prevenir ou até mesmo para amenizar tais efeitos, a recomendação frequente tem sido a prática de exercícios físicos como medida de interação terapêutica na medicina preventiva e reabilitação. Desta forma, o objetivo do presente trabalho foi avaliar os efeitos do exercício físico em ratos submetidos a dietas restritivas e hipercalóricas, através de parâmetros metabólicos, nutricionais, morfométricos e calorimétricos, além do estresse oxidativo no tecido cardíaco. Foram utilizados 32 ratos Winstar, machos, com 45 dias de idade. Os animais foram inicialmente divididos em dois grupos: G1 (n=16) considerado controle, receberam ração e água ad libitum; G2 (n=16) receberam ração em tempo restrito e solução de sacarose 30% ad libitum. Os animais de G2 receberam a mesma quantidade de ração ingerida por G1, oferecida num tempo restrito de 2 horas diárias, durante o período de 30 dias, considerado pré-treinamento. Após este período, os grupos (G1 e G2) foram subdivididos (n=8) em G3 que receberam o mesmo tratamento que G1 e os animais deste grupo foram considerados sedentários e G4 receberam o mesmo tratamento que G2 e foram considerados exercitados. Os grupos G1 e G2 foram mantidos na fase de treinamento. A natação foi utilizada como modelo de exercício, com intensidade de treinamento moderada, durante 8 semanas (fase de treinamento). O delineamento estatístico foi inteiramente ao acaso com 32 tratamentos e 8 repetições, com nível de significância de 5% de probabilidade. O consumo alimentar foi maior em G1 e G3 e menor em G2 e G4, o mesmo ocorreu para consumo de líquido. A calorimetria revela ... / Abstract: Sedentary lifestyles and poor dietary habits, such as restrictive diets hypercaloric are relevant factors to be considered. This contemporary life style, which restricts the time spent on diet and physical inactivity, especially those related to cardiovascular. To prevent or even mitigate these effects, the frequent recommendation has been the practice of physical exercise as a measure of therapeutic interaction in preventive medicine and rehabilitation. Thus, the aim of this study was to evaluate the effects of physical exercise in rats subjected to restrictive diets hypercalorific through metabolic, nutritional, morphometric and colorimetric parameters in addition to oxidative stress in cardiac tissue. 32 Winstar rats, males, 45 days old were used. Animals were divided into two groups: G1 (n=16) as the control, received food and water ad libitum, G2 (n=16) received a diet restricted in time and 30% sucrose solution ad libitum. G2 animals received the same amount of feed ingested by G1, offered in a limited time of 2 hours a day during the period of 30 days, which is considered pre-training. After this period, the two groups (G1 and G2) were subdivided (n=8), G3 receiving the same treatment as G1 and animals in this group were considered inactive and G4 received the same treatment and G2 were considered trained. G1 and G2 were maintained in the training phase. The swimming was used as a model of exercise with moderate intensity training for 8 weeks (training phase). The experimental design was completely randomized with 32 treatments and 8 replications, with a significance level of 5% probability. Dietary intake was higher in G1 and G3 and lower in G2 and G4, the same occurred for liquid consumption. Calorimetry reveals lower carbohydrate oxidation and increased lipid oxidation with high activity of β-hidroxacil-CoA dehydrogenase in G2. These animals also had higher glucose, lower HDL - cholesterol and abnormal accumulation of ... / Mestre

by Susan Sau Han Lui. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1992. / Includes bibliographical references (leaves [141]-158). / Chapter CHAPTER ONE : --- INTRODUCTION --- p.1-5 / Chapter CHAPTER TWO : --- LITERATURE REVIEW / Chapter 2.1 --- Methods of Studying Energy Intake - Dietary Assessment --- p.6-17 / Chapter 2.2 --- Energy Intake and Growth of Children --- p.18-31 / Chapter 2.2.1 --- Energy Intake and Growth Studies of Children in Other Countries / Chapter 2.2.2 --- Energy Intake and Growth Studies in Hong Kong Children / Chapter 2.3 --- Methods for Measuring Energy Expenditure --- p.31-43 / Chapter 2.3.1 --- Direct Calorimetry / Chapter 2.3.2 --- Indirect Calorimetry / Chapter 2.3.3 --- Heart Rate Method / Chapter 2.3.4 --- Doubly-labbeled Water (DLW) Method / Chapter 2.4 --- Energy Expenditure Studies in Children --- p.43-48 / Chapter 2.4.1 --- Energy Expenditure of Normal Children / Chapter 2.4.2 --- Energy Expenditure for Obese Children / Chapter 2.4.3 --- Energy Expenditure for Malnorished Children / Chapter 2.4.4 --- Other Energy Expenditure Data / Chapter CHAPTER THREE : --- A STUDY OF ENERGY INTAKE AND GROWTH FROM BIRTH TO TWO YEARS / Chapter 3.1 --- Introduction --- p.49-50 / Chapter 3.2 --- Objectives --- p.50 -51 / Chapter 3.3 --- Methodology --- p.51-69 / Chapter 3.3.1 --- The Nutritional Research Team / Chapter 3.3.2 --- Study Outline / Chapter 3.3.3 --- The Recruitment / Chapter 3.3.4 --- Study Plan / Chapter 3.3.5 --- The First and Subsequent Visits / Chapter 3.3.6 --- Measurement of Dependent Variables - Anthropometric Measurements / Chapter 3.3.7 --- Measurement of Independent Variables from Nutrient Intakes / Chapter 3.3.8 --- Other Independent Variables Considered Related to Growth Variation / Chapter 3.3.9 --- Physical and Biochemical Examination / Chapter 3.3.10 --- Data Analysis / Chapter 3.3.11 --- Summary of the approach / Chapter 3.4 --- Descriptive Results --- p.69 -84 / Chapter 3.4.1 --- Demographic Data / Chapter 3.4.2 --- General Characteristics of the Children Studied / Chapter 3.4.3 --- Growth / Chapter 3.4.4 --- Dietary Intake / Chapter 3.5 --- Result of Statistical Analysis of Variables influencing Growth --- p.84-101 / Chapter 3.5.1 --- Variables Affecting the Attained Standard Deviation Scores (Z scores) / Chapter 3.5.2 --- Variables Affecting the Change in Relative Positions of Growth Standard Deviation Scores (Z Scores) / Chapter 3.5.3 --- Variables Associated with Lower Attained Growth Standard Deviation Scores (Z scores) / Chapter 3.6 --- Discussion --- p.101 -115 / Chapter 3.6.1 --- Descriptive Data / Chapter 3.6.2 --- Whether the Variation of Growth Can be Explained by Energy Intake / Chapter 3.6.3 --- Whether the Variation of Growth Can be Explained by Other Variables / Chapter CHAPTER FOUR : --- ENERGY EXPENDITURE STUDY / Chapter 4.1 --- Introduction --- p.116 / Chapter 4.2 --- Subjects --- p.116-118 / Chapter 4.3 --- Methodology --- p.118 -123 / Chapter 4.3.1 --- Clinical and Anthropometric Assessments / Chapter 4.3.2 --- Dietary Assessment / Chapter 4.3.3 --- Assessment of Energy Expenditure / Chapter 4.4 --- Results --- p.123 -127 / Chapter 4.4.1 --- Background Characteristics / Chapter 4.4.2 --- Dietary Intake / Chapter 4.4.3 --- Energy Expenditure / Chapter 4.4.4 --- Comparison of Energy Intake and Expenditure / Chapter 4.4.5 --- Comparison with Other Studies / Chapter 4.5 --- Discussion --- p.127 -132 / Chapter 4.5.1 --- Subjects / Chapter 4.5.2 --- Energy Intake and Expenditure / Chapter 4.5.3 --- Comparison with Other Studies / Chapter 4.5.4 --- Summary / Chapter CHAPTER FIVE : --- CONCLUSIONS / Chapter 5.1 --- Pattern of Growth --- p.133 / Chapter 5.2 --- Energy Intake and Energy Expenditure of Children in Hong Kong --- p.134 / Chapter 5.3 --- Variables Affecting Growth --- p.134-136 / Chapter 5.4 --- Implications of the Study Design and Methodology 136 - --- p.138 / Chapter 5.5 --- Implication and Application of the Growth and Energy Intake Standards --- p.138-140

Objetivo. O objetivo do estudo foi analisar a influência da ingestão alimentar de proteína da soja enriquecida com isoflavona e dos exercícios com pesos sobre o metabolismo energético de mulheres na pós-menopausa. Casuística e métodos. Ensaio clínico, 16 semanas, envolvendo 60 mulheres, 59 (7) anos, distribuídas em 4 grupos: G1 (proteína da soja e exercício), G2 (placebo e exercício), G3 (proteína da soja e sem exercício) e G4 (placebo e sem exercício). A proteína da soja e o placebo (maltodextrina) foram distribuídos, aleatoriamente, sob a forma de pó, na porção de 25 gramas/dia, enriquecida com 50 mg de isoflavona. Foram 10 exercícios com pesos, realizados em 3 sessões semanais, com 3 séries de 8-12 repetições cada, carga de 60-80% de 1 repetição máxima (RM). O metabolismo energético foi analisado a partir do gasto energético de repouso (GER) e do quociente respiratório (QR). O GER foi calculado utilizando o O2 e o CO2, obtidos por calorimetria indireta (Quinton-QMC®), durante 30 minutos, sob temperatura e umidade controladas, e o QR pela relação CO2/O2. Foram utilizadas variáveis de controle: idade, hormônio folículo estimulantes (FSH), proteína e valor calórico total da alimentação (VCT), massa muscular e índice de massa corporal IMC (kg/m2). Na análise estatística foram utilizados: ANOVA, teste &#34;t&#34; de Student e regressão múltipla, por meio do software Stata 9.2, &#945;<0,05. Resultados. As mulheres apresentaram homogeneidade em todas as variáveis do estudo. Houve aumento, significante (p<0,05) do GER no G1 (158 kcal/dia) e G2 (110 kcal/dia), correspondente a 17% e 9%, respectivamente, sem alteração do QR. Não houve associação entre as variáveis de controle, com o GER e o QR, entretanto, com a intervenção, observou-se aumento significante (p<0,05) da massa muscular, G1 (7%) e G2 (10%), e da ingestão proteica, G1 (de 19 para 25%) e G3 (de 19 para 26%), sem diferença entre grupos, quanto ao VCT. Conclusão. Exercícios com pesos são determinantes para o aumento do GER de mulheres na pós-menopausa, podendo ser potencializado pela ingestão de proteína da soja enriquecida com isoflavona. / Objective. The objective of this study was analyze the influence of dietary ingestion of soy protein enriched with isoflavones and exercises with weights on energy metabolism of women in post-menopause. Material and methods. Clinical trial, 16 weeks, involving 60 women, 59 (7) years, divided into four groups: G1 (soy protein and exercise), G2 (placebo and exercise), G3 (without soy protein and exercise) and G4 (placebo and without exercise). Randomly, the soy protein and placebo (maltodextrin) were distributed in powder form; the portion of 25 grams / day was enriched with 50 mg of isoflavones. There were 10 exercises with weight, performed in three sessions per week with 3 sets of 8-12 repetitions each, with load of 60-80% of one maximum repetition (RM). The energy of metabolism was analyzed from the resting energy expenditure (REE) and respiratory quotient (RQ). The REE was calculated using the O2 and CO2, obtained through indirect calorimetry (QMC, Quinton ®) for 30 minutes under controlled temperature and humidity, and the ratio QR CO2/O2. Some variables to control the REE were used: age, follicle stimulating hormone (FSH), protein and total caloric content of food (VCT), muscle mass and body mass index - BMI (kg/m2). To the statistical analysis were used: ANOVA, &#34;t&#34; test of Student and multiple regression using the software Stata 9.2, &#945;<0.05. Results. The women presented homogeneity for all variables of the study. Significantly, there was an increase (p <0.05) of SGA in G1 (158 kcal / day) and G2 (110 kcal/ day), corresponding to 17% and 9% respectively, and no alteration of QR. Between the variables control, REE and RQ, wasnt found an association, however, through the intervention, was observed a significant (p <0.05) muscle mass, G1 (7%) and G2 (10%), and ingestion of protein, G1 (from 19 to 25%) and G3 (from 19 to 26%), with no difference among groups toward the VCT. Conclusion. The exercises with weights are crucial to the increase of REE in women in post- menopause, and can be potentiated by the ingestion of soy protein enriched with isoflavones.

A anóxia neonatal considerada relevante condição clínica mundial e vem sendo estudada no laboratório de Neurociências, ICB-USP, desde 2008. Agressões em períodos críticos de maturação do organismo, em especial do sistema nervoso, devido à sua alta demanda metabólica, podem modificar ou mesmo comprometer eventos ontogenéticos com complicações persistentes na vida adulta, sendo relacionada a retardo cognitivo e comportamental, tais como: epilepsia, déficit de atenção, hiperatividade, problemas de aprendizado, entre outros. Em ratos adultos ocorreu morte neuronal por apoptose e necrose, decréscimo da neurogênese e do volume no hipocampo após anóxia neonatal. Experimentos comportamentais evidenciaram alterações também na capacidade de aprendizagem, navegação espacial e ansiedade. Foi observado, que esse estímulo provoca retardo no desenvolvimento sensório-motor, além de ganho de peso em relação ao controle, e aumento do diâmetro rostro-caudal e naso-anal. A fim de avaliar as causas de alterações somáticas e de desenvolvimento, decidiu-se aprofundar, neste estudo, a análise da relação do hipotálamo e da leptina com as mesmas, e com o metabolismo energético assim como, com o crescimento do organismo. Para tanto, foram utilizados camundongos leptin reporters, os quais apresentam os receptores para leptina naturalmente fluorescentes. Foi adaptado modelo para indução de anóxia em camundongos machos por meio de testes de avaliação da ontogenia de reflexos; da pressão de oxigênio no sangue; da frequência cardíaca e dos níveis na Escala de Apgar. Tais testes evidenciaram prejuízos dos animais anoxiados no aparecimento dos reflexos de aceleração, geotaxia negativa, recuperação de decúbito e resposta ao susto; diminuições significativas de pressão de oxigênio e batimentos cardíacos durante período de exposição ao ambiente anóxico, além de níveis indicativos de ausência de oxigênio quando avaliados os fatores que compõe a escala de Apgar, em relação aos animais controle, validando o modelo para este estudo. Em seguida, foram analisados grupos anóxia macho e fêmea e controle macho e fêmea com relação a parâmetros corpóreos durante 60 dias de vida dos animais. Foi evidenciado que a anóxia neonatal afeta os parâmetros de maneiras distintas, porém em todas as análises, o grupo anóxia macho apresentou dimensões aumentadas em relação aos outros grupos. Quando comparada a co-localilzação de fos com receptores de leptina fluorescentes ativados, os resultados obtidos sugerem que apesar de não ter sido detectado diferença de valores de leptina circulante no sangue, houve alteração de peso corpóreo nos animais anóxia, em relação ao seu controle, o que se atribui a possível resistência dos receptores de leptina dos núcleos arqueado e dorsomedial, hipótese que deve ser explorada em experimentos futuros. / Neonatal anoxia is considered a relevant clinical condition and has been studied in the Neuroscience Laboratory, ICB-USP, since 2008. Damage caused to an organism during its maturation, particularly the damage that affects the high-metabolic nervous system, can modify or even compromise ontogenetic events with persistant complications in adulthood. Such complications are related to cognitive and behavioral retardation, and some known examples are: epilepsy, attention deficit, hyperactivity and learning problems. In adult rats, neuronal death occurs due to apoptosis, necrosis, decreased neurogenesis and decreased volume in the hippocampus after neonatal anoxia. Behavioral experiments also revealed changes in learning ability, spatial navigation and anxiety. It was also observed that neonatal anoxia causes delay in sensorimotor development, besides weight gain in relation to the control, and increase in the rostrocaudal and naso-anal diameter. In order to evaluate the causes of such somatic and developmental changes, this study analyzed the relationship between the hypothalamus and leptin, as well as their relationship with energy metabolism and the growth of the organism. Leptin reporter mice were used, which present naturally fluorescent leptin receptors. The anoxia model was adapted for male mice by means of the following tests: evaluation of the ontogeny of reflexes, the oxygen pressure in the blood, the heart rate and the levels on the Apgar Scale. These tests revealed damages to the anoxic animals by the appearance of different reflexes: acceleration, negative geotaxis, recovery of decubitus and response to scare; there was significant decrease in oxygen pressure and heart rate during exposure to the anoxic environment, in addition to levels in the Apgar scale which are indicative of oxygen absence when contrasted with control. Male and female anoxic groups and control were analyzed with respect to body parameters for a period of 60 days, and evaluated of leptin levels, Nissl staining and c-fos cell count by stereology performed. It was verified that neonatal anoxia affected the parameters in different ways, but overall the male anoxic group presented increased dimensions in relation to the other groups. Results obtained from the co-localization of fos and activated fluorescent leptin receptors suggest that, although it is not possible to observe differences in leptin values in the blood, the change in body weight of anoxic animals was due to a lack of activation of leptin receptors in arched and dorsomedial nuclei, suggesting a resistance to the effects of this hormone, hypothesis that should be explored in future experiments.

INTRODUÇÃO: A doença de Gaucher (DG) é um erro inato do metabolismo, do grupo das doenças lisossômicas, causado pela atividade deficiente da enzima glicocerebrosidase. Os tipos mais comuns da DG são o tipo I, que é o mais freqüente e não apresenta comprometimento neurológico; o II, agudo e neuropático; e o III, subagudo e neuropático. Todos os tipos caracterizam-se pela heterogeneidade clínica, com manifestações sintomáticas e de intensidade distintas, tais como hepatoesplenomegalia, alterações ósseas e hematológicas. Alguns estudos descrevem alterações metabólicas como gasto energético basal (GEB) aumentado – hipermetabolismo - em pacientes sem tratamento. A terapia de escolha para a DG é a reposição enzimática (TRE), a qual consegue reverter muitas das manifestações da doença. OBJETIVOS: 1) Avaliar o GEB por meio de calorimetria indireta em pacientes com DG do Centro de Referência do Rio Grande do Sul; 2) Avaliar o estado nutricional dos pacientes incluídos no estudo; 3) Relacionar o GEB com as condições clínicas dos pacientes. METODOLOGIA: Estudo transversal, prospectivo, controlado. Os pacientes atendidos no CRDG foram convidados a participar do estudo (n= 29), sendo que 17 concordaram (média de idade= 30,0 ± 17,2 anos, sexo masculino= 8; DG tipo III= 3 pacientes). Os pacientes com DG tipo I (n= 14; sexo masculino= 6) foram pareados por sexo, idade e índice de massa corporal (IMC) com controles hígidos para avaliação do GEB. Para determinação dos valores de VO2 e VCO2 foi utilizado um ergoespirômetro (MedGraphics Cardiorespiratory Diagnostic Systems, modelo CPX-D). Os pacientes e os controles receberam orientação prévia quanto ao jejum e o repouso e no dia da calorimetria foram pesados e medidos, sendo então calculado o IMC. Os pacientes não apresentavam outras morbidades, nem estavam em uso de medicamentos que poderiam interferir no GEB. Nas análises estatísticas, foi utilizado o GEB em kcal/kg/dia. RESULTADOS: A avaliação do estado nutricional revelou que, no grupo dos pacientes com DG tipo I, cinco estavam com sobrepeso e os demais eutróficos; no grupo com DG tipo III, dois pacientes encontravam-se desnutridos e um eutrófico. Foram realizadas 19 avaliações do GEB em 17 pacientes: dois pacientes a realizaram no período pré e após 6 meses de TRE. A média de idade e de IMC dos pacientes com DG tipo I e dos controles foi de 32,8 ± 17,6 e 32,1 ± 16,6 anos e 23,3 ± 3,1 e 22,4 ± 3,1kg/m2, respectivamente. A idade dos pacientes com DG tipo III foi, respectivamente, 12, 17 e 20 anos. Quatorze pacientes estavam recebendo TRE (média de tempo de TRE= 6,6 ± 5,3 anos; média de dose de enzima= 27,1 ± 11,7 UI/kg/inf. de imiglucerase). A média de GEB dos pacientes com DG tipo I em TRE (n= 12) foi 27,1% maior do que a dos controles (p= 0,007). O GEB de pacientes em TRE (n=12) comparado aos sem TRE (n= 4) não apresentou diferença (p= 0,92). Comparando o GEB dos pacientes em TRE e o de seus controles com o GEB estimado pela equação de Harris-Benedict, observou-se que os pacientes apresentaram GEB 6,3% maior do que o estimado (p= 0,1), enquanto que seus controles tiveram GEB 17,0% menor do que o estimado (p= 0,001). O GEB medido dos pacientes com DG tipo III foi, respectivamente, 14%, 72% e 16% maior do que o estimado pela equação de Harris e Benedict. Não foi encontrada associação significativa entre GEB e as seguintes variáveis: idade, peso, estatura, escore de gravidade, quantidade de enzima recebida, idade de início de TRE, tempo de tratamento e presença ou ausência de megalias. A correlação do GEB com o IMC foi negativa e significativa, conforme esperado. DISCUSSÃO/CONCLUSÕES: O estado nutricional classificado pelo IMC mostrou que a maior parte dos pacientes com DG tipo I estava eutrófica; no entanto, um terço apresentou pré-obesidade. Dois dos três pacientes com DG tipo III encontravam-se desnutridos. Todos os pacientes, mesmo em TRE, apresentaram um GEB significativamente maior do que os controles. A TRE não consegue normalizar o hipermetabolismo desses pacientes. / INTRODUCTION: Gaucher disease (GD) is an inborn error of metabolism of the group of lysosomal diseases, caused by the deficient activity of the glucocerebrosidase enzyme. The most common types of GD are: type I, which is the most frequent and does not present neurological compromise; type II, which is acute and neuropathic; and type III, which is subacute and neuropathic. All types are characterized by clinical heterogeneity and symptomatic manifestations of various intensity, such as hepatoesplenomegaly and bone and hematological alterations. Some studies have described metabolic alterations, such as increased basal metabolic rate (BMR), that is, hypermetabolism, in untreated patients. The therapy of choice for GD is enzyme replacement therapy (ERT), which can stop many manifestations of the disease. OBJECTIVES: 1) To evaluate BMR by means of indirect calorimetry in patients with GD seen at the Reference Center for Gaucher Disease of Rio Grande do Sul (RCGD); 2) To evaluate the nutritional status of patients included in the study; 3) To relate BMR with clinical conditions presented by patients. METHODS: The present was a prospective, controlled, cross-over study. Patients seen at the RCGD were invited to participate in the study (n=29); of these, 17 agreed to participate (mean age=30.0 ± 17.2 years, male= 8; GD type III=3 patients). Patients with GD type I (n=14; male= 6) were paired by gender, age, and body mass index (BMI) to healthy controls to evaluate BMR. To determine the values of VO2 and VCO2 an ergospirometer was used (MedGraphics Cardiorespiratory Diagnostic Systems, model CPX-D). Patients and controls received previous orientation as to fasting and resting and, on the day of the calorimetry, were weighed and measured in order for the BMI to be calculated. Patients did not present any other morbidity, neither were they making use of any medication that could interfere with BMR. In the statistical analyses, BMR in kcal/kg/day was used. RESULTS: The evaluation of the nutritional status showed that, in the group of patients with GD type I, five patients were overweight; the other were eutrophic; in the group of patients with GD type III, two patients were malnourished; one was eutrophic. Nineteen evaluations of BMR were conducted in 17 patients; two patients conducted the evaluation in the period pre-ERT and after 6 months of ERT. Mean age and mean BMI of patients with GD type I and controls were 32.8 ± 17.6 and 32.1 ± 16.6 years and 23.3 ± 3.1 and 22.4 ± 3.1kg/m2, respectively. The age of patients with GD type III was, respectively, 12, 17 and 20 years. Fourteen patients were receiving ERT (mean time of ERT=6.6 ± 5.3 years; mean enzyme dose=27.1 ± 11.7 UI/kg/inf of imiglucerase). The mean BMR of patients with GD type I on TRE (n=12) was 27.1% higher when compared to controls (p=0.007). When compared to patients not on ERT (n=4), the BMR of patients on ERT (n=12) did not show any difference (p=0.92). Comparing the BMR of patients on ERT and that of their controls with the BMR estimated by the Harris-Benedict equation, we observed that patients showed a 6.3% higher BMR than the estimated (p=0.1), while the BMR of their controls was 17.0% lower than the estimated (p=0.001). The BMR of patients with GD type III was, respectively, 14%, 72% and 16% higher than the estimated by the Harris-Benedict equation. No significant association was found between BMR and the following variables: age; weight; height; severity score; amount of enzyme received; age at beginning of ERT; time of treatment; and presence or absence of megalies. The correlation between BMR and BMI was negative and significant, as expected. DISCUSSION/CONCLUSIONS: The nutritional status classified by BMI showed that most patients with GD type I were eutrophic; however, one third of the patients showed pre-obesity. Two of the three patients with GD type III were malnourished. All patients, even on ERT, showed a significantly higher BMR when compared to controls. In conclusion, ERT was not able to normalize the hypermetabolism of these patients.

Objetivos: Quantificar o gasto energético de crianças e adolescentes com bronquiolite obliterante pós-infecciosa acompanhados em ambulatório de pneumologia pediátrica e comparar com crianças e adolescentes hígidos. Metodologia: Estudo transversal com grupo controle incluindo 72 crianças e adolescentes de 8 a 18 anos. Comparou-se dois grupos de 36 indivíduos, um com diagnóstico de BO e outro hígido, os quais foram pareados pelo gênero, idade e classificação do IMC. Para avaliação nutricional utilizou-se a antropometria e a composição corporal. O gasto energético foi medido pela calorimetria indireta; o fator atividade pelo recordatório 24h de atividades físicas e a ingestão energética pelos inquéritos alimentares. Resultados: Os resultados a seguir são apresentados, respectivamente, para o grupo BO e para o grupo controle: idade (11,8 ± 2,7) e (12,3 ± 2,8); índice de massa corporal (18,9 ± 4,0 Kg/m2) e (18,8 ± 3,4 Kg/m2); gasto energético de repouso (GER) (1717,6 ± 781,5) e (2019,9 ± 819); gasto energético total (GET) (2677,5 ± 1514,0 Kcal/dia) e (3396,1 ± 1557,9Kcal/dia); estimativa da ingestão energética (2294,1 ± 746,7Kcal/dia) e (2116,5 ± 612,1Kcal/dia). O GER e GET não foram estatisticamente diferentes entre os grupos (p= 0,102; p=0,051). O GER não foi estatisticamente diferente nem quando ajustado para massa magra (p=0,116). O GER está associado a MM (r=0,490; p0,001), sendo que quanto maior a MM, maior o gasto energético. Não houve diferenças estatisticamente significativas entre o GET e o consumo energético no grupo BO (p=0,202). O grupo controle consumiu, em média, 1.279,6Kcal a menos do que o previsto pelo GET (p<0,001). Houve diferença estatisticamente significante entre o gasto energético medido pela calorimetria indireta e o estimado pelas fórmulas de predição. Todas as fórmulas de predição subestimaram a necessidade energética. Conclusão: O GER e o GET foram semelhantes entre os grupos. A estimativa da ingestão energética das crianças e adolescentes hígidos foi menor que o GET. Os resultados sugerem que todas as fórmulas de predição utilizadas subestimaram as necessidades energéticas quando comparadas com a calorimetria indireta. / Objectives: To quantify energy expenditure in children and adolescents with post-infectious obliterans bronchiolitis (OB) receiving outpatient pediatric pulmonology care and compare them with healthy children and adolescents. Methods: Cross-sectional study with control group including 72 children and adolescents aged 8-18 years. Two groups of 36 individuals were compared – one diagnosed with OB and another healthy – which were paired as to gender, age, and body mass index classification. Anthropometry and body composition were used for nutritional assessment. Energy expenditure was measured by indirect calorimetry, activity factor was assessed through 24-hour recall, and energy intake was measured by nutrition surveys. Results: The following results are respectively presented to the OB group and to the control group: age (11.8 ± 2.7) and (12.3 ± 2.8); body mass index (18.9 ± 4.0 Kg/m2) and (18.8 ± 3.4 Kg/m2); resting energy expenditure (REE) (1717.6 ± 781.5) and (2019.9 ± 819); total energy expenditure (TEE) (2677.5 ± 1514.0 Kcal/day) and (3396.1 ± 1557.9 Kcal/day); energy intake estimate (2294.1 ± 746.7 Kcal/day) and (2116.5 ± 612.1 Kcal/day). REE and TEE were not statistically different between groups (p=0.102; p=0.051). REE was not statistically different even when adjusted for lean mass (p=0.116). REE is associated with lean mass (r=0.490; p<0.001) – the higher the lean mass, the higher the energy expenditure. There were no statistically significant differences between TEE and energy expenditure in the OB group (p=0.202). The control group had an average intake 1279.6 Kcal lower than that predicted by TEE (p<0.001). There was a statistically significant difference between energy expenditure measured by indirect calorimetry and that estimated by prediction equations. All prediction equations underestimated energy needs. Conclusion: REE and TEE weresimilar between groups. Energy intake estimate in the healthy children and adolescents was lower than TEE. Results suggest that all prediction equations used in this study underestimated the energy needs when compared with indirect calorimetry.

Objetivo. O objetivo do estudo foi analisar a influência da ingestão alimentar de proteína da soja enriquecida com isoflavona e dos exercícios com pesos sobre o metabolismo energético de mulheres na pós-menopausa. Casuística e métodos. Ensaio clínico, 16 semanas, envolvendo 60 mulheres, 59 (7) anos, distribuídas em 4 grupos: G1 (proteína da soja e exercício), G2 (placebo e exercício), G3 (proteína da soja e sem exercício) e G4 (placebo e sem exercício). A proteína da soja e o placebo (maltodextrina) foram distribuídos, aleatoriamente, sob a forma de pó, na porção de 25 gramas/dia, enriquecida com 50 mg de isoflavona. Foram 10 exercícios com pesos, realizados em 3 sessões semanais, com 3 séries de 8-12 repetições cada, carga de 60-80% de 1 repetição máxima (RM). O metabolismo energético foi analisado a partir do gasto energético de repouso (GER) e do quociente respiratório (QR). O GER foi calculado utilizando o O2 e o CO2, obtidos por calorimetria indireta (Quinton-QMC®), durante 30 minutos, sob temperatura e umidade controladas, e o QR pela relação CO2/O2. Foram utilizadas variáveis de controle: idade, hormônio folículo estimulantes (FSH), proteína e valor calórico total da alimentação (VCT), massa muscular e índice de massa corporal IMC (kg/m2). Na análise estatística foram utilizados: ANOVA, teste &#34;t&#34; de Student e regressão múltipla, por meio do software Stata 9.2, &#945;<0,05. Resultados. As mulheres apresentaram homogeneidade em todas as variáveis do estudo. Houve aumento, significante (p<0,05) do GER no G1 (158 kcal/dia) e G2 (110 kcal/dia), correspondente a 17% e 9%, respectivamente, sem alteração do QR. Não houve associação entre as variáveis de controle, com o GER e o QR, entretanto, com a intervenção, observou-se aumento significante (p<0,05) da massa muscular, G1 (7%) e G2 (10%), e da ingestão proteica, G1 (de 19 para 25%) e G3 (de 19 para 26%), sem diferença entre grupos, quanto ao VCT. Conclusão. Exercícios com pesos são determinantes para o aumento do GER de mulheres na pós-menopausa, podendo ser potencializado pela ingestão de proteína da soja enriquecida com isoflavona. / Objective. The objective of this study was analyze the influence of dietary ingestion of soy protein enriched with isoflavones and exercises with weights on energy metabolism of women in post-menopause. Material and methods. Clinical trial, 16 weeks, involving 60 women, 59 (7) years, divided into four groups: G1 (soy protein and exercise), G2 (placebo and exercise), G3 (without soy protein and exercise) and G4 (placebo and without exercise). Randomly, the soy protein and placebo (maltodextrin) were distributed in powder form; the portion of 25 grams / day was enriched with 50 mg of isoflavones. There were 10 exercises with weight, performed in three sessions per week with 3 sets of 8-12 repetitions each, with load of 60-80% of one maximum repetition (RM). The energy of metabolism was analyzed from the resting energy expenditure (REE) and respiratory quotient (RQ). The REE was calculated using the O2 and CO2, obtained through indirect calorimetry (QMC, Quinton ®) for 30 minutes under controlled temperature and humidity, and the ratio QR CO2/O2. Some variables to control the REE were used: age, follicle stimulating hormone (FSH), protein and total caloric content of food (VCT), muscle mass and body mass index - BMI (kg/m2). To the statistical analysis were used: ANOVA, &#34;t&#34; test of Student and multiple regression using the software Stata 9.2, &#945;<0.05. Results. The women presented homogeneity for all variables of the study. Significantly, there was an increase (p <0.05) of SGA in G1 (158 kcal / day) and G2 (110 kcal/ day), corresponding to 17% and 9% respectively, and no alteration of QR. Between the variables control, REE and RQ, wasnt found an association, however, through the intervention, was observed a significant (p <0.05) muscle mass, G1 (7%) and G2 (10%), and ingestion of protein, G1 (from 19 to 25%) and G3 (from 19 to 26%), with no difference among groups toward the VCT. Conclusion. The exercises with weights are crucial to the increase of REE in women in post- menopause, and can be potentiated by the ingestion of soy protein enriched with isoflavones.

N6-methyladenosine (m6A) is the most ubiquitous post-transcriptional RNA modification and has an important role in determining the fate of mRNA transcripts. Among the key proteins of the m6A pathway are methyltransferases (METTL family enzymes), demethylases (FTO, ALKBH family enzymes), and m6A binding proteins (e.g., YTHDF family) which recognize RNA sequences depending on the amount and localization of m6A in target transcripts and subsequently influence the fate of mRNA transcripts. The role of methyltransferases and demethylases is to provide a dynamic balance of m6A levels and possibly to convey mechanisms of specificity for these so-called epitranscriptomic marks, which are not yet fully understood. The main objective of this work was to determine the relative changes in the expression of key m6A pathway proteins during early postnatal development and adulthood in the rat brain. We found that the level of expression of key m6A pathway proteins decreases from birth to adulthood, with the exception of a transient increase between postnatal days 10 and 18. During this period, we also found significant changes in the expression of respiratory chain complexes. However, further research is needed to provide evidence of a mechanistic link between the m6A pathway and brain energy homeostasis during...

L'incidence des pathologies métaboliques n'a de cesse d'augmenter au cours des dernières décennies atteignant des proportions épidémiques. Les facteurs génétiques, l'alimentation et/ou la sédentarité n'expliquent qu'en partie ce phénomène. Les contaminants environnementaux sont également suspectés être impliqués dans l'étiologie de ces perturbations. Plusieurs études rapportent l'implication des récepteurs nucléaires comme médiateur de ces désordres métaboliques. Dans le cadre de ces travaux nous nous sommes intéressés aux rôles du récepteur nucléaire CAR dans la régulation de l'homéostasie énergétique et comme médiateur des perturbations métaboliques induites suite à une exposition à un mélange de pesticides. CAR est un récepteur nucléaire clé du système de détoxification de composés, qu'ils soient de nature exogène ou endogène. Son rôle sur le métabolisme énergétique a été étudié principalement chez les souris mâles, or certaines fonctions métaboliques et de détoxification sont fortement dépendantes du sexe. Le premier objectif de ces travaux a consisté à évaluer les conséquences sur l'homéostasie énergétique de la délétion du récepteur nucléaire CAR (CAR-/-) chez des souris mâles et femelles au cours du vieillissement. Les résultats montrent que l'absence de CAR est délétère chez les mâles qui développent une obésité, un diabète et une stéatose hépatique. Les souris femelles CAR-/- sont protégées de ces troubles et présentent une amélioration de leur tolérance au glucose. Cependant la suppression de leurs hormones sexuelles grâce à la réalisation d'ovariectomies enlève totalement cette protection, suggérant un rôle majeur de ces hormones dans cette protection. Les analyses du transcriptome, lipidome et métabolome hépatique sont en accord avec ces données phénotypiques. Le deuxième objectif de ces travaux a consisté à évaluer les conséquences métaboliques d'une exposition chronique in vivo à un mélange de pesticides présent dans l'alimentation à des doses supposées non toxiques. Après un an d'exposition à ce mélange, les souris mâles développent un surpoids avec une augmentation de leurs masses adipeuses. Ce surpoids s'accompagne d'une intolérance au glucose et d'une stéatose hépatique. Les souris femelles présentent, en revanche une hyperglycémie à jeun, du stress oxydatif au niveau hépatique et une perturbation de métabolites urinaires liées au microbiote intestinal. Ces résultats montrent pour la première fois un effet obésogène et diabétogène dépendant du sexe d'une exposition à un mélange de pesticides. Nous avons également mis en évidence un rôle du récepteur nucléaire CAR dans le dimorphisme sexuel observé suite à cette exposition. L'ensemble de ces travaux apporte des liens de causalité en faveur d'une relation contaminants environnementaux et santé dépendant du sexe et un rôle du récepteur nucléaire CAR dans les effets observés. Cela soulève la question de la prise en considération du sexe et de l'effet mélange dans l'évaluation des risques pour la santé liée à l'exposition à des contaminants environnementaux. / The incidence of metabolic diseases has steadily increased in recent decades reaching epidemic proportions. It is conventionally accepted that their main cause is related to a diet rich in fats and sugar and/or a sedentary lifestyle that can be aggravated by certain genetic polymorphisms. Chemical contaminants in our environment are also suspected to contribute to the development of these metabolic disorders by disrupting the energy balance of organisms. Several studies report the role of nuclear receptors as mediators of these metabolic effects induced by environmental contaminants. As part of this PhD work, we investigated the role of the CAR nuclear receptor in the regulation of energy homeostasis and as a mediator of the metabolic effects induced by exposure to a mixture of pesticides. CAR is a key nuclear receptor for the detoxification system of compounds, whether exogenous or endogenous. Its role in energy metabolism has been studied mainly in male mice, but metabolic and detoxification functions are highly dependent on sex. The first objective of this work was to evaluate the consequences on the energy homeostasis of the deletion of the CAR nuclear receptor in male and female mice. These animals were followed over a period of more than one year and their phenotype was compared to that of non-invalidated mice for this receptor. The results show that the absence of CAR is very deleterious in males that develop obesity, diabetes and hepatic steatosis. CAR-/- females mice are protected from these disorders and even have better glucose tolerance. This protection is lifted by ovariectomy of these females suggesting a role of female sex hormones in their protection. Transcriptomic, metabolomic and lipidomic analysis are in agreement with this phenotypic change. The second objective of this work was to evaluate the in vivo metabolic consequences of chronic exposure to a mixture of pesticides present in the diet at presumed non-toxic doses. After one year of exposure to this mixture, male mice developed an overweight with an increase in their fat masses. This overweight was accompanied by glucose intolerance and hepatic steatosis. On the other hand, female mice showed fasting hyperglycemia, hepatic oxidative stress and a disturbance of urinary microbiota related to the intestinal microbiota. These results show for the first time an obesogenic and diabetogenic sex-dependent effect of exposure to a mixture of pesticides. We have also demonstrated a role of the CAR nuclear receptor in the sexual dimorphism observed following this exposure. All of this work provides causal links in favor of a relationship between environmental contaminants and sex-dependent health and a role of the nuclear receptor CAR in the effects observed. This raises the issue of gender and mixture in the risk assessment linked to exposure to environmental contaminants.

Abstract not available