We are unceasingly exposed to potentially harmful microorganisms. The battle against threatening infectious agents includes activation of both the innate and of the adaptive immune systems. Illness responses are elicited and include inflammation, fever, decreased appetite, lethargy and increased sensitivity to painful stimuli in order to defeat invaders. While many of these signs of disease are controlled by the central nervous system, it has remained an enigma how signals from the peripheral immune system reach the brain through its blood-brain barrier, which precludes macromolecules, including cytokines, from diffusing into the brain parenchyma. Previous findings indicate the existence of a pathway across the blood-brain barrier, which includes binding of the cytokine interleukin-1 (IL-1) to its receptor in the brain vessels, thereby inducing the production of the prostaglandin E2 (PGE2) synthesizing enzymes cyclooxygenase-2 (Cox-2) and microsomal prostaglandin E synthase-1 (mPGES-1), which ultimately synthesize PGE2. PGE2 subsequently binds to any of the four prostaglandin E2 (EP) -receptors. Previous results from our laboratory have suggested that this pathway plays a critical role in the febrile response to infectious stimuli. The present thesis aims at further investigating the molecular events underlying immune-to-brain signalling, with special emphasis on fever, hypothalamic-pituitary-adrenal (HPA) -axis activation and anorexia and their connection to signalling molecules of the cytokine and prostaglandin families, respectively. In paper I, the molecular processes linking the proinflammatory cytokine interleukin-6 (IL-6) and PGE2 in the febrile response were investigated. Both IL-6 and PGE2 have been shown to be critical players in the febrile response, although the molecular connections are not known, i.e. if IL-6 exerts its effects up- or downstream of PGE2. Mice deficient in IL-6 were unable to respond to bacterial lipopolysaccharide (LPS) with a febrile response, but displayed similar induction of Cox-2 and mPGES-1, and similar concentrations of PGE2 in the cerebrospinal fluid as wild-type mice. Paradoxically, the IL-6 deficient mice responded with a dose-dependent elevation of body temperature in response to intracerebroventricularly injected PGE2. Furthermore, IL-6 per se was not pyrogenic when injected peripherally in mice, and did not cause increased levels of PGE2 in cerebrospinal fluid. IL-6 deficient mice were not refractory to the action of PGE2 because of excess production of some hypothermia-producing factor, since administration of a Cox-2 inhibitor in LPS-challenged IL-6 deficient mice did not unmask any hypothermic response, and neutralization of tumor necrosis factor α (TNFα), associated with hypothermia, did not produce fever in LPS-challenged IL-6 deficient mice. These data indicate that IL-6 rather than exerting its effects up- or down-stream of PGE2 affects some process in parallel to PGE2, perhaps by influencing the diffusion and binding of PGE2 onto its target neurons. In papers II and III, we injected the proinflammatory cytokine IL-1β in free-fed wild-type mice, in mice with a deletion of the gene encoding mPGES-1, or in mice deficient in the EP1, EP2 and EP3. Food intake was continuously measured during their active period, revealing that mPGES-1 deficient mice were almost completely resistant to anorexia induced by IL-1β. However, all of the investigated EP receptor deficient mice exhibited a normal profound anorexic response to IL-1β challenge, suggesting that the EP4 is the critical receptor that mediates IL-1β-induced anorexia. We also investigated the role of mPGES-1 in anorexia induced by lipopolysaccharide (LPS) in mPGES-1 deficient mice. The profound anorexic response after LPS-challenge was similar in mPGES-1 deficient and wild-type mice. To further investigate the anorectic behaviour after LPS injection, we pre-starved the animals for 22 hours before injecting them with LPS. In this paradigm, the anorexia was less profound in mPGES-1 knock-out mice. Our results suggest that while the inflammatory anorexia elicited by peripheral IL-1β seems largely to be dependent on mPGES-1-mediated PGE2 synthesis, similar to the febrile response, the LPS-induced anorexia is independent of this mechanism in free-fed mice but not in pre-starved animals. In papers IV and V, the role of prostanoids for the immune-induced HPA-axis response was investigated in mice after genetic deletion or pharmacological inhibition of prostanoid-synthesizing enzymes, including Cox-1, Cox-2, and mPGES-1. The immediate LPS-induced release of ACTH (adrenocorticotropic hormone and corticosteroids was critically dependent on Cox-1 derived prostanoids and occurred independently of Cox-2 and mPGES-1 derived PGE2. In contrast, the delayed HPA-axis response was critically dependent on immune-induced PGE2, synthesized by Cox-2 and mPGES-1, and occurred independently of Cox-1 derived enzymes. In addition, in the mPGES-1 deficient mice, the synthesis of CRH hnRNA and mRNA was decreased in the paraventricular nucleus of the hypothalamus after LPS-challenge, indicating that the delayed hormone secretion was mediated by PGE2-induced gene-transcription of CRH in the hypothalamus. The expression of the c-fos gene and Fos protein, an index of synaptic activation, was maintained in the paraventricular nucleus and its brainstem afferents both after unselective and Cox-2 selective inhibition as well as in Cox-1, Cox-2, and mPGES-1 knock-out mice. This suggests that the immune-induced neuronal activation of autonomic relay nuclei occurs independently of prostanoid synthesis and that it is insufficient for eliciting stress hormone release.

Une alimentation riche en protéines entraîne une importante diminution de la prise alimentaire, chez l’homme et l’animal, par rapport à une alimentation classique (riche en hydrates de carbones). Les précédents travaux du laboratoire chez le rat montrent que le mécanisme implique une induction de la production intestinale de glucose libéré dans la veine porte. Il s’ensuit un signal qui transite au cerveau via le nerf vague et se traduit par un effet anorexigène. Le régime protéique induit en fait une redistribution de la production endogène de glucose au profit du rein et de l’intestin chez le rat, et au profit de l’intestin et du foie chez la souris. L’effet anorexigène des protéines est présent également chez les souris, confirmant un rôle tout particulier de l’intestin, et du signal glucose portal, dans ce phénomène de satiété. Nos résultats montrent d’ailleurs que le signal glucose portal n’est pas impliqué dans l’augmentation de la production rénale de glucose induite par le régime protéique qui est observée uniquement chez le rat. Les mesures effectuées chez des rats nourris par différents régimes protéiques indiquent l’implication de mécanismes propres à la nature des protéines qui reste à déterminer. De plus nous avons mesuré une augmentation de la sensibilité à l’insuline de la production endogène de glucose chez le rat nourri par le régime protéique. Des études plus approfondies chez la souris devraient permettre de comprendre les mécanismes impliqués. Nos expériences suggèrent par ailleurs que le système mélanocortinergique ne serait pas impliqué dans l’effet anorexigène du régime à long terme mais pourrait constituer un élément important de contre-régulation face à l’hypophagie sévère temporaire provoquée par le changement de régime / Protein feeding is known to decrease hunger and subsequent food intake in animals and humans. Previous data point out the connection between the central nervous system and the intestinal glucose production in the central inhibitorycontrol of food intake by protein feeding. Our study demonstrates that protein feeding induces redistribution of endogenous glucose production to the kidney and intestine in rats and to the intestine and liver in the mouse. Anorexigenic effect of protein diet exists in both animal models, confirming a specific role of the intestine in this satiety phenomenon. Moreover, portal glucose sensing is not involved in the induction of renal glucose production by protein feeding that is only observed in rats. Measurement in rat fed with different protein diets suggest a role of the nature of the protein or structure, but proper mechanisms remain to be clarified. Moreover, protein feeding potentiates the endogenous glucose production suppression by insulin. Some additional studies have to be performed to find the mechanisms that are implicated. Our experiments suggest that the melanocortinergic system wouldn’t be involved in the longterm anorexigenic effect of protein feeding but could constitute an important counter-regulatory pathway against the temporary hypophagia induced by diet change

Eating disorders are serious psychological disorders associated with debilitating lifestyle, multiple health problems and high rates of suicidality and mortality. Despite extensive research, the aetiology of eating disorders still remains unclear. Amongst the identified risk factors for eating disorders, stress has been frequently studied. The purpose of the present study was to explore the possibility that tail-pinch administered to rats could provide an animal model of stress-induced eating disturbances in humans, and whether environmental enrichment might ameliorate the effects of stress. In Experiment 1, we compared eating behaviours of rats that were reared in either enriched or standard environments and later exposed to tail-pinch and allowed to eat when food deprived. The study showed that a single exposure to tail-pinch induced eating disturbances in most of the rats. When rats were not food deprived, but were conditioned to eating when placed in test chamber, tail-pinch suppressed eating in all rats, but significantly more for rats reared under standard than in enriched conditions. Experiment 2 used a between-subjects design in which rats were reared in either a standard or enriched environment, and were either exposed to tail-pinch or not exposed during sessions in which they were not food deprived and allowed to eat. Tail-pinch suppressed the food intake of rats reared in enriched but not standard environments. Although this finding appeared to contradict results of Experiment 1, analysis of body weight revealed that exposure to tail pinch suppressed increases in weight gain across sessions more for rats reared in standard than enriched environments. The suppression of food intake during test sessions for enriched but not standard rats exposed to tail-pinch was attributed to differences in contextual conditioning and discrimination of the test chamber from home cages. Overall, results of the present study suggest that rats reared in enriched environments were more resilient to the effects of tail-pinch as a stressor. Implications of these findings for the understanding of human eating disorders are discussed.

Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro / Esta tese é composta por quatro artigos que permitiram avaliar o impacto do consumo de alimentos fora do domicílio na dieta e no peso corporal da população brasileira. O primeiro artigo revisou de forma sistemática as evidências científicas da associação entre alimentação fora do domicílio e peso corporal com abordagem crítica dos artigos publicados na literatura. Foram avaliados 28 artigos e os resultados sugeriram uma associação positiva entre o consumo de alimentos fora do domicílio e o ganho de peso. A revisão mostrou que uma das limitações nessa área é a ausência de padronização nas definições e métodos de avaliação do consumo de alimentos fora do domicílio. Para o desenvolvimento dos demais artigos, utilizou-se dados do Inquérito Nacional de Alimentação (INA) do Brasil, uma subamostra da Pesquisa de Orçamentos Familiares (POF) 2008-2009, com o objetivo de caracterizar o consumo de alimentos fora do domicílio da população brasileira (artigo 2) e investigar a associação entre alimentação fora do domicílio e ingestão total de energia (artigo 3) e peso corporal (artigo 4). As análises foram realizadas com os dados de consumo de alimentos coletados por meio de registro alimentar de 34.003 indivíduos acima de 10 anos em dois dias não-consecutivos. Os registros incluíram descrição detalhada dos alimentos e quantidade consumida, tipo de preparação, horário e local de consumo (dentro ou fora do domicílio). Alimentação fora do domicílio foi definida como todo alimento adquirido e consumido fora de casa. O primeiro dia de registro foi utilizado nas análises, considerando o peso amostral específico do INA e o efeito do desenho amostral. O consumo de alimentos fora do domicílio no Brasil foi reportado por 40% dos entrevistados; diminuiu com a idade e aumentou com a renda em todas as regiões brasileiras; foi maior entre os homens e na área urbana. Os grupos de alimentos com maior percentual de consumo fora de casa foram bebidas alcoólicas, salgadinhos fritos e assados, pizza, refrigerantes e sanduíches. Entre indivíduos residentes nas áreas urbanas do Brasil (n=25.753), a média de energia proveniente dessa alimentação foi 337 kcal, representando 18% do consumo total de energia. Alimentação fora do domicílio foi positivamente associada ao consumo total de energia. Avaliando somente adultos entre 25 e 65 anos de idade das áreas urbanas (n=13.736) não foi encontrada associação entre o consumo de alimentos fora do domicílio e Índice de Massa Corporal (IMC). Indivíduos que consumiram alimentos fora do domicílio apresentaram menor ingestão de proteína; maior ingestão de gordura total, gordura saturada e açúcar livre; menor consumo de arroz, feijão e leite e maior consumo de salgadinhos fritos e assados, doces e açúcar, refrigerantes e bebidas alcoólicas do que não consumidores. Apesar da ausência de associação entre alimentação fora de casa e excesso de peso, o consumo de alimentos fora do domicílio influencia a qualidade da dieta dos indivíduos e em longo prazo pode ter um impacto no ganho de peso da população, portanto, deve ser considerado nas ações de saúde pública voltadas para a melhoria da alimentação dos brasileiros. / This thesis is composed by four articles that focused on the impact of food consumed away from home on the diet and body weight of the Brazilian population. The first article is a systematic review of the scientific evidence of the association between food away from home and body weight with a quality assessment of published articles in scientific literature. We evaluated 28 articles and results suggested a positive association between the consumption of food away from home and weight gain. The review showed that one of the limitations in this area is the lack of standard definition and methods to assess away-from-home eating. For the other articles, data from the Brazilian National Dietary Survey (NDS) conducted along with the Household Budget Survey (HBS) 2008-2009 were used to characterize the consumption of food away from home (article 2); to investigate the association between away-from-home food consumption and total energy intake (article 3), and body weight (article 4). Analyses were conducted with 34,003 individuals over 10 years old with data on food intake collected through food records in two non-consecutive days. The records included detailed description of the food and the amount consumed, type of preparation, and time and place of consumption (at home or away from home). Away-from-home food was defined as all foods purchased and consumed outside the home. The first day of record was used in the analyses, taking into account the sample weight of NDS and the sample design. The consumption of food away from home in Brazil was reported by 40% of the respondents; decreased with age and increased with income in all Brazilian regions; it was higher among men and in urban areas. The groups with the highest percentage of food consumption outside the home were alcoholic beverages, baked and deep-fried snacks, pizza, soft drinks and sandwiches. Among those living in urban areas (n=25,753), the mean energy intake from away-from-home food was 337 kcal, accounting for 18% of total energy intake. Food away from home was positively associated with total energy intake. Evaluating only adults between 25 and 65 years old in urban areas (n=13,736), we found no association between the consumption of food away from home and Body Mass Index (BMI). Individuals who consumed food away from home had a lower intake of protein, higher intake of total fat, saturated fat, and free sugar, low consumption of rice, beans and milk and higher consumption of baked and deep-fried snacks, sweets and sugar, soft drinks, and alcoholic beverages than non-consumers. Despite the lack of association between eating out and being overweight, the consumption of food away from home influences diet quality and in long-term it can have an impact on weight gain of the population. Therefore, it should be considered in public health strategies aiming at improving the diet of Brazilian population.

Bakgrund: Demens är en obotlig sjukdom. Demenssjukdom kan leda till allvarliga symtom som språksvårigheter, minnesdysfunktion och beteendeförändringar. Detta bidrar till att personer med demenssjukdom kräver en särskild och väl anpassad omgivning. Personer med demenssjukdom behöver trygghet i sin vardag, vilket blir en viktig uppgift för sjuksköterskan. I omvårdnadsarbetet ska sjuksköterskan sträva efter att öka välbefinnandet hos patienter. I detta fall utforma omgivningen i matsalen utifrån patienters förutsättningar. Syfte: Att beskriva måltidsmiljöns utformning och hur den påverkar personer med demenssjukdom. Metod: En litteraturöversikt har genomförts. Elva kvantitativa vetenskapliga artiklar har använts till studien. Artiklarna har valts ut från databaserna CINAHL och PubMed som svarar på syftet. Artiklarna analyserades enligt Fribergs analysmetod för att kunna slutföras som material till resultatet. Resultat: Resultatet redovisas utifrån ett tema; omgivningen kring patienter när de äter och tre subtema; musikens betydelse vid måltidssituationen; belysningens betydelse vid måltidssituationen; betydelsen av en hemlik matsal. Dessa beskriver olika resurser som visade sig öka välbefinnandet hos patienter med demenssjukdom. Diskussion: Måltidsmiljön hade en stor inverkan på personer med demenssjukdom. Omgivningen i matsalen anpassades utifrån patientens förutsättning. Den förändrande måltidsmiljön ökade patientens välbefinnande. Hemlik miljö, lugn bakgrundsmusik och tillräcklig belysning under måltiden hade en stor betydelse för patienten. Den positiva effekten kunde bidra till ökat kaloriintag och minskad negativ beteende hos patienter. / Background: Dementia is an incurable disease. Dementia can lead to serious symptoms such as language difficulties, dysfunction and behavioral changes. People with dementia need a special and well-suited environment. People with dementia need security in their daily lives, which becomes an important task for the nurse. In nursing work, the nurse will aim to increase the wellbeing of patients. In this case, the environment is designed in the dining room based on the patient's conditions. Aim: To describe the design of the meal environment and how it affects people with dementia. Method: A literature review has been carried out. Eleven quantitative scientific articles have been used for the study. The articles have been selected from the CINAHL and PubMed databases corresponding to the purpose. The articles have been analyzed with Friberg’s analysis method to be completed as material for the result. Results: The result is based on a theme; the environment around the patients when they eat and three subtemes; the importance of music in the meal situation; the importance of lighting in the meal situation; the meaning of a home-like dining room. These describe the various resources required to increase the well-being of patients with dementia. Discussion: The meal environment had a major impact on people with dementia. The environment in the dining room was adapted to the patient's requirements. The changing meal environment increased patient wellbeing. The home-like environment, calm background music and sufficient lighting during the meal were of great importance to the patient. The positive effect could contribute to increased calorie intake and decreased negative behavior in patients.

Made available in DSpace on 2015-07-22T20:50:53Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-08-31 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Associação Fundo de Incentivo à Psicofarmacologia (AFIP) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Introdução: A complexidade da fisiopatologia na Esteatose Hepática Não Alcóolica (EHNA) envolve uma interface entre as adipocinas e a regulação neuroendócrina do balanço energético, incluindo o papel do sistema Neuropeptídeo Y/Proteína agouti relacionada. Objetivo: estabelecer a relação entre a razão NeuropeptídeoY/Proteína relacionada Agouti (AgRP) e a adiponectinemia, bem como avaliar a influência de neuropeptídeos orexígenos nos aspectos nutricionais de adolescentes obesos com EHNA submetidos a uma intervenção interdisciplinar de longo prazo. Métodos: Recrutou-se adolescentes obesos pós-púberes para participarem de uma intervenção interdisciplinar. O grupo foi analisado de acordo com a presença ou não de EHNA pela ultrassonografia (US). As amostras de sangue foram coletadas para a mensuração da glicemia, transaminases hepáticas e perfil lipídico, resistência e sensibilidade insulínica. As concentrações de Adiponectina, NPY e AgRP foram avaliadas por ELISA e a mensuração da gordura visceral e subcutânea pela US. A ingestão alimentar foi aferida por meio de registro alimentar de 3 dias. Resultados: No início da terapia, observou-se que parâmetros clínicos importantes como massa corporal, IMC, gordura visceral, HOMA-IR, QUICKI, triglicérides, VLDL-colesterol e transaminases hepáticas apresentaram-se mais alterados em pacientes com EHNA, os quais melhoram após tratamento. Além disso, a energia total e ingestão de macronutrientes reduziram significativamente em ambos os grupos. Observou-se correlação positiva entre AgRP e a gordura visceral em todos os pacientes, e correlação negativa entre NPY/AgRP com a concentração de adiponectina apenas em adolescentes obesos com EHNA. Ao analisar a influência da dieta nos neuropeptídeos orexígenos, apenas os pacientes com EHNA apresentaram correlação positiva entre a ingestão de ácidos graxos saturados com os neuropeptídeos orexígenos (NPY e AgRP); e carboidrato com NPY. Foi observada correlação positiva entre ingestão de energia, (%) de lipídio e ácidos graxos saturados com o acúmulo de gordura visceral. Conclusão: Os pacientes com EHNA apresentaram parâmetros clínicos mais alterados ao compará-los àqueles que não possuíam esta doença, incluindo a correlação negativa entre adiponectina e NPY/AgRP. Estes resultados sugeriram que adolescentes obesos com EHNA apresentaram perfil inflamatório alterado, o qual pode influenciar na regulação neuroendócrina do balanço energético indicando uma barreira adicional na terapia de redução de peso. Além disso, nossos achados revelaram uma importante influência da composição da dieta no sistema orexígeno, sendo essencial considerar a ingestão excessiva de gordura saturada como um fator determinante para o desenvolvimento de EHNA. / BACKGROUND: The complexity physiophatology in the Non Alcoholic Fatty Liver Disease (NAFLD) involves interplay between adipokines and neuroendocrine regulation of energy balance, including the role of Neuropeptide Y/Agouti Related Protein system. AIM: establishing the relationship between Neuropeptide Y/Agouti Related Protein (NPY/AgRP) ratio and adiponectinemia, as well as to assess the influence of orexigenic neuropeptides in the nutritional aspects of NAFLD obese adolescents submitted to a long-term interdisciplinary approach. METHODS: A group of post-pubescent obese adolescents were recruited and included in the interdisciplinary intervention. The group was analyzed according to the presence or ausence of NAFLD by ultrassonography (US). Blood samples were collected to measure glycemia, hepatic transaminases and lipid profile, insulin resistance and sensitivity. Adiponectin, NPY and AgRP concentrations were measured by ELISA and the measurement of visceral ans subcutaneous fat by US. Food intake was measured using 3-day diet records. RESULTS: It was observed at baseline that important clinical parameters including body weight, BMI, visceral fat, HOMA-IR, QUICKI, triglycerides, VLDL-cholesterol and hepatic transaminases were more altered in NAFLD patients. After the intervention, these parameters, total energy and macronutrient intake were reduced significantly in both groups. The most important finding was the positive correlation between AgRP with visceral fat in all patients, and negative correlation between NPY/AgRP with adiponectin only in NAFLD obese adolescents. Analyzing the influence of the diet in the orexigenic neuropeptides, only the NAFLD patients presented a positive correlation between the saturated fatty acids intake and the orexigenic neuropeptides (NPY and AgRP); and carbohydrate with NPY. Indeed, it was observed a positive correlation between energy intake, lipid (%) and saturated fatty acids with visceral fat accumulation. CONCLUSION: NAFLD patients presented more altered clinical parameters than non-NAFLD, including the negative correlation between adiponectin and NPY/AgRP. These results suggested that NAFLD obese adolescents presented an altered inflammatory profile that can influence the neuroendocrine regulation of energy balance suggesting and additional impairment in the weigth loss therapy. Moreover, our findings showed an important influence of diet composition in the orexigenic system, being essential consider that the excessive saturated fatty acids intake could be a determinant factor to increase nonalcoholic fatty liver disease. / FAPESP: 2008/53069-0 / FAPESP: 2006/00684-3 / FAPESP (CEPID/Sono): 9814303-3 / TEDE

No description available.

Orientador: Maria Rita Marques de Oliveira / Resumo: A obesidade é resultante de uma complexa interação entre fatores genéticos, ambientais e metabólicos, cujo controle dos casos extremos tem se realizado com cirurgia. Embora efetivos, os resultados da cirurgia são variáveis e pouco se sabe sobre os efeitos em longo prazo. Objetivo: avaliar o efeito tardio da cirurgia bariátrica considerando técnica cirúrgica, consumo alimentar e as variações de peso, diante de um desfecho clínico desejável e indesejável. Métodos: Este estudo prospectivo não concorrente envolveu a participação de 74 mulheres (idade 42,2 ± 6,2 anos; IMC 44,7 ± 6,5 kg/m2) submetidas à cirurgia de derivação gástrica em Y-Roux (DGYR). Os pacientes foram categorizados em dois grupos de acordo com a variação de peso pós-cirúrgica: Grupo 1 – variação ≤10% do menor peso alcançado (desfecho desejável); Grupo 2 – reganho de peso >10% do menor peso alcançado (não desejável). Foram avaliados peso corporal, % perda do excesso de peso (%PEP), peso mínimo atingido, presença de comorbidades, consumo de energia e macronutrientes e Baros. Resultados: Após 6 anos da cirurgia, 35/74 pacientes apresentaram reganho de peso >10% do menor peso atingido (Grupo 2). Os grupos eram homogêneos para variáveis pré-cirúrgicas. A mediana do menor peso atingido para os pacientes do Grupo 1 foi de 74 (67,8 - 80) kg e 71,4 (64,6 – 80,8) Kg para os pacientes do Grupo 2, alcançados em 24 (18 – 42) e 18 (12 – 24) meses, respectivamente (p=0,017). O %PEP dos pacientes do Grupo 1 foi de 77% e 66% para... (Resumo completo, clicar acesso eletrônico abaixo) / Mestre

A puberdade é uma fase do desenvolvimento marcada pelo surgimento de características sexuais secundárias e que culmina na capacidade reprodutiva do organismo. A puberdade inicia com a ativação dos neurônios que expressam o peptídeo hormônio liberador de gonadrotrofinas (GnRH), que resulta em modificação do padrão de liberação do hormônio luteinizante (LH) pelos gonadotrofos, e aumento da produção gonadal de 17β-estradiol (E2). O sistema kisspeptidérgico, composto pelo peptídeo kisspeptina (KiSS-1) e o receptor de kisspeptina (KiSS1r), parece ser um dos responsáveis pela ativação dos neurônios que secretam GnRH para o início da puberdade. Alguns trabalhos sugerem que esse sistema é modulado por sinais periféricos que sinalizam o estado de desenvolvimento e reserva de energia do organismo, como o fator de crescimento semelhante à insulina-1 (IGF-1) e o hormônio leptina, respectivamente. Estudos em humanos sustentam que há um adiantamento da idade de início da puberdade em meninas, atribuindo o excesso de adiposidade como um possível fator causal. Em condições de excesso de tecido adiposo, as concentrações de leptina e IGF-1 estão aumentadas, sugerindo que estes fatores possam exercer modulação sobre o sistema kisspeptina e adiantar a instalação da puberdade. Assim, o presente estudo analisou a ingestão alimentar e o desenvolvimento de obesidade sobre a instalação da puberdade e a participação de fatores-chave para a instalação da puberdade em fêmeas de rato Wistar alimentadas com Dieta de Cafeteria a partir do desmame. Foram utilizadas fêmeas de rato Wistar desmamadas aos 21 dias de vida. Os animais foram alocados para o grupo Controle (ração padrão e água ad libitum) e grupo Dieta de Cafeteria (alimentos processados consumidos por humanos). Diariamente, os animais foram inspecionados para a abertura vaginal (indicador de instalação da puberdade) e a ingestão alimentar foi monitorada. No dia da abertura vaginal, os animais foram decapitados e o encéfalo e sangue foram coletados e armazenados. Nas amostras contendo a Banda Diagonal de Broca e hipotálamo foi analisada a expressão dos genes Gnrh1, Kiss1, Kiss1r e Lepr. No soro, quantificou-se a concentração de LH, E2, leptina e IGF-1. Também foram dissecados e pesados o tecido adiposo intraabdominal, o útero, os ovários e as adrenais. Os resultados revelaram aumento da ingestão de energia e lipídeos e adiantamento da abertura vaginal no grupo Dieta de Cafeteria. O peso dos ovários foi aumentado pela Dieta de Cafeteria, embora o peso do útero e o peso das adrenais não tenham sido alterados. Esses animais tiveram menor peso corporal, porém com aumento do tecido adiposo intra-abdominal e da concentração de leptina, ambos associados entre si e com o dia da abertura vaginal no grupo Dieta de Cafeteria. A Dieta de Cafeteria não alterou a concentração sérica de LH e E2 no dia da abertura vaginal. O tratamento com Dieta de Cafeteria não modificou a expressão de Gnrh1 mRNA, Kiss1 mRNA e Kiss1r mRNA, porém aumentou a expressão de Lepr mRNA em amostras contendo a Banda Diagonal de Broca e hipotálamo. A maior concentração de leptina não foi correlacionada com a maior expressão de Lepr mRNA. Os resultados sugerem que a introdução precoce de alimentos processados pode alterar o padrão fisiológico de ingestão alimentar e estimular o desenvolvimento do tecido adiposo intra-abdominal e a liberação de leptina. Um limiar de concentração de leptina parece ser um elemento permissivo para a instalação da puberdade em condições controle, porém uma elevação precoce pode estimular os reguladores fisiológicos e adiantar o início da puberdade. / Puberty is a stage of development marked by the appearance of secondary sexual characteristics, culminating in the achievement of reproductive capacity. Some observational studies support the notion that there is an early onset of puberty in girls related to obesity. Puberty starts with the activation of gonadotrophin-releasing hormone (GnRH) neurons, which stimulate the release of luteinizing hormone (LH) by gonadotrophs, and increased gonadal production of 17β-estradiol (E2). The kisspeptidergic system, comprising the kisspeptin peptide (KiSS-1) and the kisspeptin receptor (KISS1R), seems to activate GnRH neurons and puberty onset. The kisspeptidergic system is modulated by peripheral signals related to the body energy storage, such as the insulin-like growth factor 1 (IGF-1) and the leptin. In an obesity situation, the levels of leptin and IGF-1 are increased, suggesting that these factors may exert modulation of the kisspeptidergic system and the puberty onset. Thus, this study examined the effect of obesity on puberty onset in female rats and the expression of key genes (GnRH, kisspeptin and its receptor) and its potential regulators (leptin, IGF-1 and E2). Wistar female rats weaned at 21 days were allocated to the Control group (chow and water ad libitum) or to the Cafeteria Diet group (processed foods consumed by humans). Every day, the animals were inspected for vaginal opening (puberty onset signal) and the food intake was measured. On the day of vaginal opening, the animals were decapitated and the brain and blood were collected and stored. Expression of genes Gnrh1, Kiss1, Kiss1r and Lepr were analyzed in the collected brains by qPCR. Serum LH, E2, leptin and IGF-1 were analyzed by ELISA. Intra-abdominal adipose tissue, the uterus, the ovaries and adrenal glands were also dissected and weighed. The results have shown higher energy and fat intake and early vaginal opening in the Cafeteria Diet group. The ovarian weight was increased by the Cafeteria Diet, although the weight of the uterus and adrenal have not changed. These animals demonstrated lower body weight, but with increased intra-abdominal adipose tissue and high leptin levels, both associated with each other and with the day of vaginal opening in Cafeteria Diet group. The Cafeteria Diet has not changed serum LH and E2 on the day of vaginal opening. Treatment with Cafeteria Diet has not changed the expression of Gnrh1 mRNA, Kiss1 mRNA and Kiss1r mRNA, but increased the expression of Lepr mRNA in brain samples from Diagonal Band of Broca and hypothalamus. The higher concentration of leptin was not associated with the increased expression of Lepr mRNA. The results suggest that early access to processed foods can change the physiological pattern of food intake and stimulate the development of obesity and the release of leptin. A leptin threshold appears to be a permissive factor for puberty onset under control conditions, but it may overlap other physiological regulators and trigger early puberty onset in obesity conditions.

Introdução: Epilepsia é uma desordem cerebral caracterizada predominantemente pela interrupção paroxística do funcionamento normal do cérebro causada por crises epilépticas que ocorrem de maneira recorrente e imprevisível. Aproximadamente 50% dos adultos com epilepsia têm ao menos uma comorbidade médica associada, e algumas condições apresentam uma prevalência maior quando comparados à população em geral. Entre elas podemos citar as comorbidades psiquiátricas e as alterações nutricionais. Objetivos: O presente estudo avaliou o consumo alimentar de pacientes portadores de epilepsia, e de forma mais específica, o consumo dos ácidos graxos poli-insaturados (PUFAS), e a sua relação com a presença de transtornos neuropsiquiátricos. Métodos: Foi realizado um estudo transversal onde o consumo alimentar de paciente com epilepsia do lobo temporal foi avaliado por um questionário de frequência alimentar (QFA) validado para a população de Porto Alegre –RS. Também foi avaliado a presença de transtornos psiquiátricos e sintomas de ansiedade através dos questionários estruturados, SCID, BAI e Escala de Hamilton. Resultados: Pacientes com diagnóstico de transtornos psiquiátricos avaliado por SCID apresentaram menor consumo de ácidos graxos omega-3, (0,53 ± 0,34g vs 0,84 ± 0,58g; p=0,047) e (0,21g ± 0,13g/1000kcal vs 0,32±0,21g/1000kcal; p=0,049). Pacientes com maiores níveis de ansiedade avaliados pelo BAI também apresentaram menor ingestão de PUFAS n-3 (9,14 ± 3,65g vs 12,82 ± 4,84g; p=0,011 e 3,41 ± 1,21% vs 4,14 ± 1,05% do VET; p=0,04). A Escala de Hamilton apresentou correlação inversa ao consumo de PUFAS n-3 (-0,306; p=0,041). Conclusão: Foi identificada uma associação entre o consumo de PUFAS n-3 e a presença de transtornos psiquiátricos e níveis mais altos de ansiedade em pacientes com epilepsia do lobo temporal. Ainda que o nosso estudo não pode determinar uma relação de cause efeito entre alterações neuropsiquiátricas e consumo de PUFAS é possível que um consumo de alimentos ricos em Omega-3 possa ser uma estratégica terapêutica a fim de melhorar anormalidades neuropsiquiátricas nesses pacientes. Essa é uma interessante questão que necessita ser melhor avaliada no futuro. / Background: Epilepsy is a brain disorder characterized by recurrent and unpredictable interruptions of normal brain function. About 50% of the adults patients with epilepsy have one or more coexisting medical conditions. Among the comorbidities, we highlight nutritional problems as well psychiatric disorders, which have a significant impact in the life quality of this patient. Aims: The aim of this study is to evaluate the nutritional intake of lobe temporal epilepsy patients and investigate its relation with psychiatric disorders diagnosis. Patients and Methods: we performed a cross-sectional study with 45 temporal lobe epilepsy patients and applied a food frequency questionary (FFQ), comparing the results with psychiatric diagnosis assessed by SCID to any disorders and depression by BAI and Hamilton Scale for anxiety. Results: All patients had a higher consumption of calories (38,89 ± 15,44). than the preconized for people in general and a lower intake of PUFAS than the recommended for cardiovascular protection. Patients identified with any psychiatric disorder by SCID had a lower intake of PUFAS n-3 (0,53 ± 0,34g vs 0,84 ± 0,58g; p=0,047 and 0,21g ± 0,13g/1000kcal vs 0,32±0,21g/1000kcal; p=0,049 than those free of diagnosis. Patients with high levels of anxiety also had also had a lower consumption of PUFAS n-3 (9.14 ± 3.65g vs 12.82 ± 4,84g; p=0.011). The Hamilton Scale had a negative correlation with PUFAS n-3 intake (0,306; p=0,041). Conclusion: We found a negative relation between the diagnosis of psychitric disorders and anxiety as assessed by SCID and BAI respectively. It’s not possible to determine a cause and effect relationship in this association, but we can consider the omega-3 fat acid and PUFAS n-3 rich food might be potentially therapeutic in patients with temporal lobe epilepsy. This question might deserve further studies.