O comportamento de escolha é entendido como a seleção de uma entre duas ou mais alternativas disponíveis, diferente da preferência, que está relacionada ao tempo despendido respondendo a uma dessas alternativas. Em pesquisas com não humanos, observa-se que os sujeitos escolhem com maior frequência as alternativas nas quais o reforço estará disponível de forma imediata, em pequena quantidade, em comparação com a alternativa na qual o reforço estará disponível somente depois que o animal esperar um tempo determinado (atraso), mas em maior quantidade. Apesar da literatura apresentar dados sobre a influência da restrição alimentar e do sexo do animal em tarefas de aprendizagem, é importante aprofundar a investigação desses aspectos em tarefas de escolha. O objetivo desta pesquisa foi comparar o desempenho de ratos Sprague Dawley (machos e fêmeas) com história de restrição alimentar e ratos controle (com comida ad libitum), em uma tarefa de escolha, em que as alternativas variavam em relação ao atraso para ter acesso à comida e à quantidade de comida disponível. Foram utilizados 24 ratos (12 machos), de linhagem Sprague-Dawley, divididos em dois grupos. O Grupo Controle (C) recebeu dieta ad lib., enquanto o Grupo Restrição (R) teve sua dieta restrita a 80% da dieta do grupo controle. Aos 70 dias de idade, houve uma subdivisão dos grupos: metade dos animais do Grupo C formou o Grupo Controle-Restrito (CR 80% da dieta), e a outra metade o Controle-Controle (CC 100% da dieta). No Grupo R, metade dos animais formou o Grupo Restrito-Controle (RC 100% da dieta) e a outra metade, o Grupo Restrito-Restrito (RR 80% da dieta). Na Etapa 1 os animais exploravam labirinto em U em uma sessão de 10 tentativas. Na Etapa 2 foram realizadas 10 sessões de 16 tentativas de escolha forçada, sendo oito no braço direito, onde havia seis pelotas de ração disponíveis após atraso de 15 s (alternativa LL), e oito no braço esquerdo, com três pelotas de ração disponíveis sem atraso (alternativa SS). Na Etapa 3, foram conduzidas 45 sessões com 30 tentativas (10 forçadas e 20 livres), para verificar o padrão de escolha dos animais dos diferentes grupos em função da disponibilidade de reforço em cada alternativa, do atraso em uma das alternativas e do tempo inicial de espera (tempo T). Os animais de todos os grupos apresentaram preferência pela alternativa SS, independente do sexo ou da dieta. Ao comparar a porcentagem de escolhas dos grupos com relação às dietas foram verificadas diferenças no padrão e nas latências médias de escolha. O grupo RR apresentou latências médias de escolha significativamente inferiores às do grupo CC e um estabelecimento mais rápido de preferência pela alternativa SS que o grupo CC. Apesar de não terem sido encontradas diferenças significativas entre machos e fêmeas nos parâmetros analisados (possivelmente em função do n amostral), verificou-se que fêmeas apresentaram latências menores que machos em todos os grupos, além de porcentagens de escolha pela alternativa SS maiores que os machos. São discutidas hipóteses sobre a influência da dieta e da quantidade de alimento disponível em cada alternativa sobre as escolhas dos grupos. Essas hipóteses são também relacionadas a aspectos evolutivos, referentes às funções desempenhadas por machos e fêmeas na natureza. / The behavior of choice is understood as the selection of between two or more alternatives available, different from the preference, which is related to the time spent by responding to one of these alternatives. In researches with non-human animals, it is observed that the subjects choose more frequently the alternatives on which the reinforcement will be available immediately, in small quantity, in comparison with the alternative in which the reinforcement is available only after the animal expects a certain time (delay), but in greater quantity. Although literature present data on the influence of food restriction and the sex of the animal in tasks of learning, it is important to deepen the investigation of these aspects in tasks of choice. The objective of this research was to compare the performance of rats Sprague Dawley (male and female) with a history of food restriction and control rats (with food ad libitum), in a task of choice, in that the alternatives varied in relation to the waiting time for access to food and the quantity of food available. 24 albino rats (12 males), from Sprague-Dawley lineage was used, divided in two groups. The Control Group (C) received diet ad lib., while the group restriction (R) had their diet restricted to 80% of the diet of the control group. At 70 days of age, there was a subdivision of the groups: half of the animals from group C formed the Group Controle-Restrito (CR - 80% of the diet), and the other half the Controle-Controle (CC - 100% of the diet). In Group R, half of the animals formed the Group Restrito-Controle (RC - 100% of the diet) and the other half, the Restrito-Restrito group (RR - 80% of the diet). In Step 1 the animals explored the labyrinth in U in a session of 10 attempts. In Step 2, there were 10 sessions of 16 attempts of forced choice, being 8 in the right arm, where there were six pellets of ration available after delay of 15 s, and eight in the left arm with three pellets of rations without delay. In Step 3, 45 sessions were conducted with 30 attempts (10 forced and 20 free), tarry check the default choice of animals of different groups in relation to the availability of strengthening in each alternative, the delay in one of the alternatives and the initial time wait time (T). Animals of all groups have preference for the SS alternative, independently of sex or diet. Differences were verified in the pattern and average latencies of choices in comparing the percentage of choices of the groups in relation to the diets. The RR group presented significantly lower average latency in comparison to group CC and a faster preference was established for alternative SS than group CC. Even having no significant differences been found between males and females in the scope studied (possibly due to then sampling), it was verified that females present lower latencies that males in all groups, besides the higher percentages for choosing alternative SS in males. Hypotheses are discussed on the influence of the diet and the quantity of food available in each alternative over the group choices. These hypotheses are also related to evolutionary aspects, referent to functions performed by males and females in nature.

O comportamento de escolha é entendido como a seleção de uma entre duas ou mais alternativas disponíveis, diferente da preferência, que está relacionada ao tempo despendido respondendo a uma dessas alternativas. Em pesquisas com não humanos, observa-se que os sujeitos escolhem com maior frequência as alternativas nas quais o reforço estará disponível de forma imediata, em pequena quantidade, em comparação com a alternativa na qual o reforço estará disponível somente depois que o animal esperar um tempo determinado (atraso), mas em maior quantidade. Apesar da literatura apresentar dados sobre a influência da restrição alimentar e do sexo do animal em tarefas de aprendizagem, é importante aprofundar a investigação desses aspectos em tarefas de escolha. O objetivo desta pesquisa foi comparar o desempenho de ratos Sprague Dawley (machos e fêmeas) com história de restrição alimentar e ratos controle (com comida ad libitum), em uma tarefa de escolha, em que as alternativas variavam em relação ao atraso para ter acesso à comida e à quantidade de comida disponível. Foram utilizados 24 ratos (12 machos), de linhagem Sprague-Dawley, divididos em dois grupos. O Grupo Controle (C) recebeu dieta ad lib., enquanto o Grupo Restrição (R) teve sua dieta restrita a 80% da dieta do grupo controle. Aos 70 dias de idade, houve uma subdivisão dos grupos: metade dos animais do Grupo C formou o Grupo Controle-Restrito (CR 80% da dieta), e a outra metade o Controle-Controle (CC 100% da dieta). No Grupo R, metade dos animais formou o Grupo Restrito-Controle (RC 100% da dieta) e a outra metade, o Grupo Restrito-Restrito (RR 80% da dieta). Na Etapa 1 os animais exploravam labirinto em U em uma sessão de 10 tentativas. Na Etapa 2 foram realizadas 10 sessões de 16 tentativas de escolha forçada, sendo oito no braço direito, onde havia seis pelotas de ração disponíveis após atraso de 15 s (alternativa LL), e oito no braço esquerdo, com três pelotas de ração disponíveis sem atraso (alternativa SS). Na Etapa 3, foram conduzidas 45 sessões com 30 tentativas (10 forçadas e 20 livres), para verificar o padrão de escolha dos animais dos diferentes grupos em função da disponibilidade de reforço em cada alternativa, do atraso em uma das alternativas e do tempo inicial de espera (tempo T). Os animais de todos os grupos apresentaram preferência pela alternativa SS, independente do sexo ou da dieta. Ao comparar a porcentagem de escolhas dos grupos com relação às dietas foram verificadas diferenças no padrão e nas latências médias de escolha. O grupo RR apresentou latências médias de escolha significativamente inferiores às do grupo CC e um estabelecimento mais rápido de preferência pela alternativa SS que o grupo CC. Apesar de não terem sido encontradas diferenças significativas entre machos e fêmeas nos parâmetros analisados (possivelmente em função do n amostral), verificou-se que fêmeas apresentaram latências menores que machos em todos os grupos, além de porcentagens de escolha pela alternativa SS maiores que os machos. São discutidas hipóteses sobre a influência da dieta e da quantidade de alimento disponível em cada alternativa sobre as escolhas dos grupos. Essas hipóteses são também relacionadas a aspectos evolutivos, referentes às funções desempenhadas por machos e fêmeas na natureza. / The behavior of choice is understood as the selection of between two or more alternatives available, different from the preference, which is related to the time spent by responding to one of these alternatives. In researches with non-human animals, it is observed that the subjects choose more frequently the alternatives on which the reinforcement will be available immediately, in small quantity, in comparison with the alternative in which the reinforcement is available only after the animal expects a certain time (delay), but in greater quantity. Although literature present data on the influence of food restriction and the sex of the animal in tasks of learning, it is important to deepen the investigation of these aspects in tasks of choice. The objective of this research was to compare the performance of rats Sprague Dawley (male and female) with a history of food restriction and control rats (with food ad libitum), in a task of choice, in that the alternatives varied in relation to the waiting time for access to food and the quantity of food available. 24 albino rats (12 males), from Sprague-Dawley lineage was used, divided in two groups. The Control Group (C) received diet ad lib., while the group restriction (R) had their diet restricted to 80% of the diet of the control group. At 70 days of age, there was a subdivision of the groups: half of the animals from group C formed the Group Controle-Restrito (CR - 80% of the diet), and the other half the Controle-Controle (CC - 100% of the diet). In Group R, half of the animals formed the Group Restrito-Controle (RC - 100% of the diet) and the other half, the Restrito-Restrito group (RR - 80% of the diet). In Step 1 the animals explored the labyrinth in U in a session of 10 attempts. In Step 2, there were 10 sessions of 16 attempts of forced choice, being 8 in the right arm, where there were six pellets of ration available after delay of 15 s, and eight in the left arm with three pellets of rations without delay. In Step 3, 45 sessions were conducted with 30 attempts (10 forced and 20 free), tarry check the default choice of animals of different groups in relation to the availability of strengthening in each alternative, the delay in one of the alternatives and the initial time wait time (T). Animals of all groups have preference for the SS alternative, independently of sex or diet. Differences were verified in the pattern and average latencies of choices in comparing the percentage of choices of the groups in relation to the diets. The RR group presented significantly lower average latency in comparison to group CC and a faster preference was established for alternative SS than group CC. Even having no significant differences been found between males and females in the scope studied (possibly due to then sampling), it was verified that females present lower latencies that males in all groups, besides the higher percentages for choosing alternative SS in males. Hypotheses are discussed on the influence of the diet and the quantity of food available in each alternative over the group choices. These hypotheses are also related to evolutionary aspects, referent to functions performed by males and females in nature.

No description available.

Mitochondrial uncoupling proteins (UCPs) belong to the superfamily of mitochondrial anion-carriers. The longest known is UCP1, predominantly expressed in brown adipose tissue, where it takes part in nonshivering thermogenesis. In the late 1990s were discovered other sequence homologs of UCP1 with tissue specific distribution. The Function of these "new" uncoupling proteins is still uncertain. It is assumed that each of the isoforms has a specific function depending on the type of tissue. This thesis showed differences in tissue transcription pattern between rat and mice using RT-PCR absolute quantification. Significant differences in pattern were found in lungs, brain and muscle. In each case UCP expression was higher in mice tissues. Mice lungs express mainly UCP2. The difference in mice brain is caused by ucp4 and ucp5 genes transcription and finally in muscle is highest content of UCP3 mRNA. We investigated whether any of ucp transcript can complement ucp2 transcripton in spleen or lungs of ucp2 -/- mice. We did not find any difference which can explain, that in isolated lung mitochondria of fasted ucp2-/- mice were uncoupled in state 4. In the last project, we found relationship between ucp2 transcription in insulinoma INS-1E cells and oxygen levels of the cultivation atmosphere.

Made available in DSpace on 2016-04-29T13:17:53Z (GMT). No. of bitstreams: 1 Beatriz Azevedo Moraes.pdf: 2597554 bytes, checksum: fbe5f48c5153f3acb37c26e3e5e3fb43 (MD5) Previous issue date: 2014-03-28 / The objective of this work was to investigate the eating behavior of three women who underwent bariatric surgery and propose an intervention for the control of food restriction and the intermittent access to palatable foods as a strategy to change an eating pattern said to be compulsive. Participated in this research three women who agreed to record their daily food ingestion, through an electronic self-monitoring and photo taking during four phases. The first, Baseline, was performed to assess the initial dietary pattern. In Phase 2, the participants were given tokens to exchange for gift cards, in case the electronic record was corresponding to the photo, to ensure the reliability of the record. In Phase 3.1, besides the reinforcement for correspondence, the participants were instructed to eat every three hours and in case of following this guidance, they would also receive the tokens. In Phase 3.2, the instruction and reinforcement were designed for the preparation and intake of a palatable portion of food of up to 150 kcal. During Phase 4, the suspension of the intervention occurred, and only the selfmonitoring and the photo were kept. Among the 3 participants, one (P3) interrupted her participation before the start of Phase 2. The results showed that for P1 and P2, binge eating during Baseline was classified by the quality and quantity of food ingested and after the intervention only the eating behavior before a certain quality of food (sugars and fats) seemed to have been evocative for the binge reporting. The data also showed the change of eating habits of P1 and P2, once the intervals between meals decreased and both began to ingest palatable foods in a more continuous and limited way. This change coincides with the decrease in the report of episodes said to be compulsive, indicating that the variables that the study aimed to alter seem, in fact, to be related to the improper eating behavior of the participants / O objetivo da presente pesquisa foi investigar o comportamento alimentar de três mulheres que realizaram a cirurgia bariátrica e propor uma intervenção para o controle da restrição alimentar e do acesso intermitente à alimentos palatáveis como estratégia de mudança do padrão alimentar dito compulsivo. Participaram da pesquisa três mulheres que concordaram em registrar diariamente sua alimentação, através de um automonitoramento eletrônico e da foto durante quatro fases. A primeira, Linha de Base, foi realizada para avaliar o padrão alimentar inicial de cada participante. Na Fase 2 as participantes receberam fichas para trocar por um vale-compras, caso o registro eletrônico fosse correspondente à foto, de forma a garantir a fidedignidade do registro. Na Fase 3.1, além do reforçamento para a correspondência, as participantes receberam instruções para se alimentar de três em três horas e caso seguissem a orientação também recebiam fichas. Na Fase 3.2, a instrução e o reforçamento foram delineados para a preparação e ingestão de uma porção diária de alimento palatável de até 150kcal. Durante a Fase 4, ocorreu a suspenção da intervenção, sendo mantido apenas o automonitoramento e a foto. Das 3 participantes, uma (P3) interrompeu sua participação antes do início da Fase 2. Os resultados mostraram que para P1 e P2 a compulsão alimentar durante a Linha de Base foi classificada através da qualidade e da quantidade de alimento ingerida e após a intervenção apenas o comportamento alimentar diante de determinada qualidade dos alimentos (açucares e gorduras) parece ter sido evocativa para o relato de compulsão. Os dados também apontaram a mudança dos hábitos alimentares de P1 e P2, uma vez que os intervalos entre as refeições diminuíram e ambas passaram a ingerir alimentos palatáveis de forma mais contínua e limitada. Esta mudança coincide com a diminuição no relato de episódios ditos compulsivos, indicando que as variáveis que o estudo se propôs a alterar parecem estar, de fato, relacionadas com o comportamento alimentar inadequado das participantes

L’obésité abdominale est associée à de nombreuses complications métaboliques, telles que la résistance à l’insuline, le diabète de type 2 et les maladies cardiovasculaires. Récemment, il a été suggéré que ces anomalies métaboliques sont étroitement associées à la taille des adipocytes, cellules constitutives du tissu adipeux. En effet, plusieurs travaux suggèrent que plus les adipocytes sont gros, plus ils produisent des adipokines pro-inflammatoires, responsables de l’inflammation chronique associée à l’obésité. Dans ce contexte, le but de ce travail de thèse était, dans un premier temps, d’établir les répartitions en fréquences de tailles des adipocytes dans différentes situations physiologiques et physiopathologiques et dans différents dépôts adipeux à l’aide du Multisizer IV Coulter counter et dans un second temps de corréler la taille des adipocytes à leurs fonctions physiologiques. D’une part, nous avons montré que quels que soient les dépôts adipeux, les répartitions en fréquences de tailles des adipocytes ont toutes le même profil, elles sont bimodales avec une population de petits adipocytes (diamètre < nadir) et une population de gros adipocytes (diamètre > nadir). La privation en insuline (diabète de type I) entraînant une diminution de 60% de la masse du tissu adipeux, altére profondément la répartition bimodale en fréquences de tailles des adipocytes. La supplémentation en insuline de ces animaux diabétiques restaure la cellularité du tissu adipeux et la répartition en fréquences de tailles des adipocytes, suggérant un rôle régulateur majeur de l’insuline sur ces paramètres. La restriction calorique partielle, nous a permis de mettre en évidence un phénomène d’hystérésis dans certains tissus adipeux. De plus, à partir des données de restriction calorique prolongée il a été possible d’établir un modèle prédisant la cinétique des changements de tailles des adipocytes et de la répartition en fréquences de tailles. D’autre part, après avoir séparé les adipocytes en deux populations : les gros (diamètre > 50 µm) et les petits adipocytes (diamètre < 50 µm) nous avons montré que les petits adipocytes sont plus sensibles à l’insuline que les gros. Nous avons aussi constaté que les gros adipocytes sont plus lipolytiques que les petits adipocytes. Ces données sont en accord avec le modèle établi montrant que les échanges avec le micro-environnement tissulaire sont surtout dépendants de la surface des membranes cellulaires. Ainsi, nos résultats mettent en évidence que si la quantité de tissu adipeux est importante, sa qualité, dont la répartition en fréquences de tailles des adipocytes, est également importante et pourrait servir de paramètre prédictif du développement des désordres métaboliques. / Abdominal obesity is associated with several metabolic complications such as insulin resistance, type 2 diabetes and cardiovascular diseases. Recently, it has been suggested that these metabolic abnormalities are closely related to the size of adipocytes, cells constituting adipose tissue. Indeed, numerous studies suggested that the more adipocytes are larger, the more they produce pro-inflammatory adipokines which are responsible for obesity-associated chronic inflammation. In this context, the aim of this work was, in the first time, to establish the size frequency distributions of adipocytes in different physiological and pathological situations and in different fat depots using the Coulter counter Multisizer IV, and in the second time to correlate the size of the adipocytes to their physiological functions. On the one hand, we have shown that, all adipocyte size frequency distributions have the same profile regardless of fat depots, they are bimodal with both the population of small adipocytes (diameter < nadir) and the population of large adipocytes (diameter > nadir). Deprivation of insulin (type I diabetes) resulting in a decrease of 60% of adipose tissue mass, profoundly alters the bimodal distribution of adipocyte size frequency. Insulin supplementation of these diabetic animals restores cellularity of adipose tissue and the size-frequency distribution of adipocytes, suggesting a major regulatory role of insulin on these parameters. Partial caloric restriction has allowed us to a hysteresis phenomenon in some adipose tissues. In addition, following data from extended caloric restriction it has been possible to develop a model predicting the kinetic of changes concerning both the size of adipocytes and the frequency distribution. On the other hand, after separating the adipocytes in two populations: large (diameter > 50 microns) and small adipocytes (diameter < 50 microns), we have shown that small adipocytes are more insulin-sensitive than large ones. We also observed that larger adipocytes are more lipolytic than smaller ones. These data are in agreement with the established model showing that the interactions with the tissue microenvironment are mainly dependent on the surface of cell membranes. Thus, our results show that if the amount of adipose tissue is important, the quality which noticed by the adipocyte size frequency distributions is also important and could be used as a marker to predict the development of metabolic disorders.

Orientador: José de Anchieta de Castro e Horta Júnior / Resumo: A associação do baixo peso ao nascer com alto risco de doenças como obesidade, diabete tipo 2 e doenças cardiovasculares na vida adulta levaram à hipótese da “Origem Desenvolvimentista da Saúde e Doença” (DOHaD). Nessa hipótese, Programação se refere às adaptações executadas pelo organismo frente a insultos ocorridos durante seu desenvolvimento, gerando efeitos permanentes ou não na estrutura e função de órgãos. A nutrição materna durante o desenvolvimento do indivíduo é considerada um importante indutor de Programação, visto que a deficiência de nutrientes, durante a prenhez e a lactação, provoca alterações significativas no peso corpóreo, no balanço energético, na ingestão alimentar e na expressão de neuropeptídeos. O hormônio concentrador de melanina (MCH) e o transcrito regulado pela cocaína e anfetamina (CART) são neuropeptídeos expressos na área hipotalâmica lateral (LHA), que participam da regulação do balanço energético e do comportamento alimentar, nos quais o MCH desempenha papel orexígeno e o CART, anorexígeno. Nosso objetivo foi analisar o número e a distribuição de neurônios MCH e CART e sua ultraestrutura na LHA de ratos cujas mães foram submetidas à restrição alimentar durante a prenhez e lactação. Fêmeas prenhes Wistar foram separadas em dois grupos experimentais: grupo controle (GC), dieta padrão ad libitum, e grupo restrição calórica (GR), dieta de 50% de restrição em relação ao grupo controle durante os períodos de prenhez e lactação. Foram avaliados o núme... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The association between lower birth weight and an increased risk of obesity, diabetes type 2 and cardiovascular diseases in adult life led to Developmantal Origins of Health and Disease (DOHaD) hypothesis. In this hypothesis, programming is related to the adjustments performed by the organism to insults occurring at key stages of their development, which may lead to long-lasting effects in the organs structure and function. Maternal nutrition during critical periods of individual development is considered an important Programming inductor, since the nutrient deficiency during pregnancy and lactation causes significant changes in body weight, energy balance, food intake and neuropeptides expression. The melanin-concentrating hormone (MCH) and the cocaine- and amphetamine-regulated transcript (CART) are neuropeptides expressed in the lateral hypothalamic area (LHA) that are involved in the regulation of energy balance and feeding behavior in which MCH plays an orexigenic role and CART an anorexigenic one. Thus, our aim was to analyze the number and the distribution of MCH and CART and the ultrastructure of these neurons in the LHA of rats whose mothers were subjected to food restriction during pregnancy and lactation. After pregnancy confirmation, female Wistar rats were divided in two groups: control group (CG), ad libitum standard diet, and caloric restriction group (RG), 50% diet restriction compared to the control group during pregnancy and lactation. After birth, the numbe... (Complete abstract click electronic access below) / Doutor

Le but de ce travail était de déterminer les effets de la pratique d'activité physique sur le phénotype osseux et l'adiposité médullaire en cas d'insuffisance pondérale selon deux approches complémentaires, chez l'humain et chez les souris. La première étude a été menée sur 24 femmes normo-pondérées et 13 femmes en sous-poids âgées entre 20 et 35 ans. Cette étude a montré que les femmes en sous-poids présentent une faible masse osseuse au niveau du corps entier, rachis lombaire et col fémoral et une altération de la géométrie du col fémoral par rapport aux femmes normo-pondérées, et un score de l'os trabéculaire sur la limite inférieure de la normale. La VO₂ₘₐₓ (L/min) était parmi les principaux déterminants des paramètres osseux chez les jeunes femmes quel que soit leur indice de masse corporelle. Les résultats de cette première étude suggèrent que l'augmentation de la VO₂ₘₐₓ (L/min) sont essentiels pour prévenir la perte osseuse chez les jeunes femmes en sous-poids. La deuxième étude a été menée sur des souris femelles jeunes adultes soumises à un exercice physique volontaire dans une roue combinée à une restriction alimentaire (restriction de 50% de l'apport ad libitum) pendant 15 et 55 jours. Cette étude a démontré que la perte pondérale liée à la restriction alimentaire présente des répercussions négatives sur l'os cortical avec peu d'effets néfastes sur l'os trabéculaire et est associée à une augmentation du nombre des adipocytes médullaires dès 15 jours de restriction. Cette étude a également démontré que l'exercice physique volontaire dans une roue ne protège pas contre les modifications de l'architecture osseuse et l'accumulation de l'adiposité médullaire liées à la restriction alimentaire. Parce que la ghréline est apparue comme régulateur potentiel de l'adiposité médullaire, la troisième étude a été menée sur des souris femelles jeunes adultes dépourvues du récepteur de la ghréline (Growth Hormone Secretagogue Receptor, Ghsr-/-) soumises à une restriction alimentaire (restriction de 50% de l'apport ad libitum) combinée à un exercice physique volontaire dans une roue de 21 jours. Cette étude a démontré que la ghréline est un médiateur clé de l'expansion de l'adiposité médullaire associée à la restriction alimentaire suite à l'activation du GHSR et que la restriction alimentaire est nécessaire pour révéler certaines différences dans la microarchitecture osseuse associée à l'invalidation du GHSR. / The aim of this work was to determine the effects of physical activity on bone phenotype and bone marrow adiposity in underweight conditions using two complementary approaches, on human and on mice. The first study was conducted on 24 normal weight women and 13 underweight women aged 20-35 years. This study showed that underweight women have appropriately lower bone mass at the whole body, lumbar spine and femoral neck and altered femoral neck geometry compared to normal weight women, and a trabecular bone score on the lower limit of normal. VO₂ₘₐₓ (L/min) was considered as strong determinant of bone parameters in young adult women regardless of their body mass index. The results of this first study suggest that increasing VO₂ₘₐₓ (L/min) is essential to prevent bone loss in underweight young women. The second study was conducted on young adult female mice subjected to voluntary wheel running and food restriction (50% of ad libitum intake) during 15 and 55 days. This study demonstrated that weight loss related to food restriction has a negative impact on cortical bone with few adverse effects on trabecular bone and is associated with an increase in the number of bone marrow adipocytes already after 15 days of restriction. This study also showed that voluntary wheel running exercise does not protect against changes in bone architecture and accumulation of bone marrow adiposity related to food restriction. Because ghrelin appeared as a potential regulator of bone marrow adiposity, the third study was conducted on young adult mice lacking the ghrelin receptor (Growth Hormone Secretagogue Receptor, Ghsr-/-) subjected to voluntary wheel running and food restriction (50% of ad libitum intake) during 21 days. This study demonstrated that ghrelin is a key mediator of food restriction - associated bone marrow adiposity expansion through activation of GHSR and that food restriction is necessary to reveal some differences in bone microarchitecture associated to GHSR invalidation.

No description available.

Estudos hodológicos sugerem um dimorfismo sexual das projeções da área incerto-hipotalâmica (IHy), com áreas relevantes para o controle reprodutivo mais densamente inervadas em fêmeas. Estudos funcionais mostraram que o RNAm do precursor do hormônio concentrador de melanina (ppMCH) varia apenas na IHy, durante o ciclo estral e é reduzido em ratas em anestro induzido por restrição alimentar (RA). Nosso objetivo foi analisar em camundongos fêmeas, as alterações na morfologia de útero e ovários e na expressão do RNAm do ppMCH da IHy ocasionadas pelo anestro induzido por RA. Para isso, camundongos fêmeas C57BL/6 foram distribuídas em controle (C), restrito (R; ração = 70% do C) e realimentado (RR). Os animais R foram perfundidos após 4, 8 e 12 dias para coleta de encéfalo, útero e ovários. Houve um aumento no número de folículos antrais nos animais R12 comparados ao R4 e redução da área uterina nos animais R8 com recuperação dos RR. Não foi possível detectar alterações na expressão do RNAm do ppMCH na IHy. / Hodological studies suggest a sexual dimorphism of the incerto-hypothalamic area (IHy) projections since relevant areas to the reproductive control are more densely innervated in females. Functional studies have shown that the MCH precursor mRNA (ppMCH) varies only in the IHy during the estrous cycle of an intact rat and is decreased in anestrus rats induced by food restriction. We aim to analyze, in female mice, the changes in uterine and ovarian morphology and expression of IHy ppMCH mRNA in anestrus induced by food restriction. For this, C57BL/6 female mice were distributed in control (C), food restricted (FR) and refed (RR). FR were perfused after 4, 8 and 12 days to collect the brain, uterus and ovaries. Our results show an increased number of antral follicles of R12 compared to R4 and a reduction in the uterine area of R8 with restoration in RR. It was not possible to detect changes in ppMCH mRNA expression in IHy.