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CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Sirtuins (SIRTs) are a protein family with high preservation degree among evolutionary scale. SIRTs are histone deacetylases regulatory enzymes of genetic material deeply involved in numerous physiological tasks including metabolism, brain function and aging. Mammals sirtuins comprise seven enzymatic components (SIRT1–SIRT7). The highest studied sirtuin is SIRT1, which plays an essential position in the prevention and evolution of neuro-disorders. Resveratrol (3,5,4-trihydroxystylbene) (RSV) is a polyphenol, which belongs to a family compounds identified as stilbenes, predominantly concentrated in grapes and red wine. RSV is the must studied Sirtuin activator and is used as food supplementary compound. Resveratrol exhibits strong antioxidant activity, reducing free radicals, diminishing quinone-reductase-2 activity and exerting positive regulation of several endogenous enzymes. Resveratrol is also able to inhibit pro-inflammatory factors, reducing the stimulation of the nuclear factor kB (NF-kB) and the release of endogenous cytokines. Resveratrol treatment can modulate multiple signaling pathway effectors related to programmed cell death, cell survival, and synaptic plasticity. In this context, the present review looks over news and the role of Sirtuins activation and resveratrol effects on modulating target genes, cognition and neurodegenerative disorders.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Scope: this study has a novel approach to investigate the effects of oral supplementation of kefir grains on metabolic improvement and the expression of the antioxidant enzymes Glutathione Peroxidase (GPx) and Catalase (CAT) of the liver in malnourished mice. Method and results: swiss mice were divided into four groups and subjected to two treatment phases: the food restriction phase of 20% in relation to the control group was maintained until animals reached a weight deficit of about 20% in relation to their original weight and the renutrition phase, the animals received diets every day for 30 days. Diets (chow powder plus kefir grains) were administered orally. Thereafter, during throughout the experiment measurements of body weight and energy consumption were obtained. After the end of treatment, fasting glucose tolerance tests were performed at night and insulin sensitivity with fed mice. Soon in then, the mice were euthanized by beheading in guillotine and the blood and liver were collected for evaluation of biochemical parameters, Histopathological assessments and Reverse transcriptase (RT-PCR). Conclusion: the present study demonstrated the kefir grains ability to modulate inflammation and hepatic oxidative-stress under malnourished-state.

Objetivo: compreender a depressão na terceira idade, o perfil e o processo de prevenção e tratamento dos sinais e sintomas. Metodologia: a revisão integrativa de literatura foi feita utilizando as bases: Biblioteca Virtual da Saúde (BVS): Sistema Latino Americano e do Caribe de informação em Ciências da Saúde (LILACS), Scientific Electronic Library Online (Scielo). Foram escolhidos os estudos científicos publicados nos últimos 10 anos, epublicados na íntegra, no período de 2007 a 2017. Foram utilizados os seguintes termos: “Depressão em idosos”; “Sintomas de Depressão”; “Prevenção da Depressão” e “Tratamento da Depressão”. Resultados: após confrontarmos os resultados encontrados com a revisão da literatura que a depressão no idoso é um dos transtornos psiquiátricos mais frequentes. Acredita-se que conforme o aumento da idade, mais sintomas depressivos são apresentados, através das queixas intensificadas de doenças e a presença do quadro de ansiedade. Para melhor qualidade o idoso necessita ter conhecimento sobre sua condição e as doenças que podem lhe acometer, o que a auxilia na promoção da própria saúde, reduzindo o sofrimento. Contribuindo para o envelhecimento ativo, tornando-a participativa na sociedade, onde demonstra autonomia sobre a própria velhice. Considerações finais: evidenciou-se a partir da literatura que existe a necessidade de agir de modo preventivo, junto aos idosos, é premente. A prática e o desenvolvimento de atividades de lazer têm-se mostrado na vida dos idosos como um fator de grande importância. O lazer contribui para um melhor estado de espírito e no caso dos mais idosos, diminui os efeitos decorrentes do processo de envelhecimento. Objective: to understand depression in the elderly, the profile and the process of prevention and treatment of signs and symptoms. Methodology: integrative literature review was done using the bases: Virtual Health Library (VHL): Latin American and Caribbean System of information in Health Sciences (LILACS), Scientific Electronic Library Online (Scielo). At the end of the search, the scientific studies published in the last 10 years, published in full, between 2007 and 2017 were selected. The following terms were used: "Depression in the elderly"; "Symptoms of Depression"; "Prevention of Depression" and "Treatment of Depression". Results: after comparing the results found with the literature review that depression in the elderly is one of the most frequent psychiatric disorders. It is believed that as the age increases, more depressive symptoms are presented, through intensified complaints of illness and the presence of anxiety. For better quality the elderly need to know about their condition and the diseases that can affect him, which helps him to promote his own health, reducing suffering. Contributing to active aging, making it participatory in society, where it demonstrates autonomy over one's own old age. Final considerations: it has been evidenced from the literature that there is a need to act in a preventive way, together with the elderly, it is urgent. The practice and development of leisure activities have been shown in the lives of the elderly as a factor of great importance. Leisure contributes to a better state of mind and, in the case of the elderly, reduces the effects of the aging process.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Objective: the increased prevalence of obesity and associated comorbidities, such as cardiovascular and metabolic diseases, has gained attention worldwide, and the renin-angiotensin system (RAS) has been pointed out as a possible link. Thus, the present study aimed to verify the possible association between angiotensinogen (AGT) or angiotensin-converting enzyme (ACE) polymorphisms with overweight and obesity in adults. Subjects and methods: the present investigation was a population-based cross-sectional study including 1,567 individuals from an urban area in Brazil. Anthropometric, clinical and biochemical parameters were evaluated, and all individuals were genotyped for the ACE I/D and AGT M/T polymorphisms. Results: the prevalence of overweight was higher among men, whereas obesity was more prevalent among women. However, the frequency of ACE or AGT polymorphisms was similar among body mass index (BMI) categories. In addition, the mean age-adjusted BMI averages did not change significantly for ACE or AGT polymorphisms, regardless of sex or BMI category. The age-adjusted BMI average for the combination of ACE and AGT genotypes evidenced no significant differences regardless of sex or BMI categories. Results were similar when BMI was replaced by waist circumference (WC). Conclusions: we were not able to find any associations between BMI and WC (overweight/obesity) and ACE and AGT polymorphisms, indicating that the RAS system might not be involved in overweight and obesity, at least based on genetic backgrounds. However, further studies must measure RAS components to elucidate this question.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Objective: because the impact of conditioned fear stress on apical bone resorption is unknown, the aim of the current studywas to use a rat model to evaluate the impact of conditioned fear stress on the bone resorption of inflammatory apical periodontitis lesions. Methods: twenty-five animals were divided into two groups. They underwent a surgical procedure in the first left lower molar tooth to expose the dental pulp and induce inflammatory apical periodontitis lesions through the retention of contamination (bacterial infection) during a 56-day period. The animals in the case group were stressed daily by using electrical stimuli (1.10 mA), whereas the animals in the control group were absent from the stressful stimuli (shocks). The open field test was performed to validate the stress methodology. The jaws were removed and collected for histological and radiographic analyses. Results: stressed animals presented increased levels of bone loss and inflammatory cells in the root apex in comparison with the control group (P = 0.0001). However, no radiographic differences were observed between the groups (P > 0.05). Conclusions: our results demonstrated that conditioned fear stress could modify a periapical lesion by increasing the size of bone loss there. Conditioned fear stress also increased the total number of inflammatory cells compared with the control group. Studies evaluating the impact of conditioned fear stress on human periapical inflammatory lesions should be encouraged.

Made available in DSpace on 2022-04-29T08:45:22Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-12-15 White adipose tissue (WAT) dysfunction and obesity are a consequence of a low-grade inflammation state. These WAT irregularities could result from abnormal metabolic renin-angiotensin system (RAS) control. Recently, tributyltin (TBT) has been found to play a critical role in these metabolic irregularities. However, TBT actions on the WAT-RAS functions are not currently well understood. In this study, we assessed whether TBT exposure resulted in metabolic syndrome (MetS) development and other metabolic complications as a result of abnormal modulation of WAT-RAS pathways. TBT (100 ng/kg/day) was administered to adult female Wistar rats, and their WAT morphophysiology and adipokine profiles were assessed. We further assessed the expression of Angiotensin-II receptor proteins (AT1R and AT2R) and proteins involved in downstream pathways mediating inflammation and adipogenesis modulation. TBT-exposed rats exhibited increases in body weight and adiposity. TBT rats present dyslipidemia and insulin resistance, suggesting MetS development. TBT promoted WAT inflammatory infiltration, AT1R protein overexpression and reduced Angiotensin-(1–7) expression. These TBT WAT abnormalities are reflected by NFκB activation, with higher adipokine levels (leptin, TNF-α and IL-6) and overexpression of AKT, ERK, P38, FAS and PPARγ protein. In vitro, TBT exposure stimulates lipid accumulation, reduces AT2R protein expression, and increases leptin, AKT and ERK protein expression in 3T3L1 cells. These findings suggest that TBT exposure participates in MetS development via the improper function of WAT-RAS metabolic control. Department of Morphology Healthy Sciences Center Federal University of Espírito Santo Department. of Food Science Faculty of Pharmacy Federal University of Minas Gerais Department of Pharmacology Biological Sciences Institute Federal University of Minas Gerais Department of Internal Medicine Botucatu School of Medicine University of São Paulo State Dept. of Basic Nursing Nursing School Federal University of Minas Gerais Health Science Graduate Program UNIMONTES Institute of Agricultural Sciences Food Engineering College Federal University of Minas Gerais Laboratório de Endocrinologia e Toxicologia Celular Programa de Pós-Graduação em Ciências Fisiológicas/CCS Universidade Federal do Espírito Santo, Av. Marechal Campos, 1468, Prédio do básico I, sala 5

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Outra Agência Radiation Therapy (RT) is a treatment option for a large number of neoplasias. However, the effect of RT on the level of hypoxia markers is poorly understood. The present study aimed to investigate the effect of RT on the levels of hypoxic markers in Oral squamous cell carcinoma (OSCC). Evaluation of HIF-1α and miR-210 levels in OSCC was performed. Then a proteomic analysis was performed to identify candidate hypoxic targets of RT. To validate proteomic studies, the effect of RT on HIF-1α, miR-210, PDH-A and LDH-A levels under hypoxia was assessed by qRT-PCR. The impact of RT in hypoxia markers was evaluated in patients to confirm in vitro results. An increase in the HIF-1α levels was observed in OSCC. RT reduced OSCC cell proliferation and migration. Interestingly, hypoxia could revert the effect of radiation on OSCC phenotype. However, proteomics analyses suggested that LDH is one of the critical targets of RT even in hypoxia. Moreover, RT decreased HIF-1α, miR-210, and LDH even in hypoxia. The current study demonstrated that hypoxia could revert the effects of RT in the OSCC context. However, RT reduces the levels HIF-1α, miR-210 and LDH in vivo and in vitro. The consequences of RT in blood should be carefully investigated.

Background: the renin-angiotensin system (RAS) is a critical contributing factor to obesity and related diseases. Several studies have shown the relationship of obesity with cyclooxygenase-2. Objectives: based on these facts, we aimed to investigate the celecoxib oral administration (a selective anti-inflammatory inhibitor of cyclooxygenase-2 (ICOX-2)) effects, in mice fed a high-fat diet by assessing the renin-angiotensin system and inflammatory markers expression. Methods: FVB/N male mice were divided into 3 groups and fed with experimental diets, standard, high-fat diet and high-fat diet plus ICOX-2 at a dose of 100mg/kg/body weight. Body weight, food intake, blood parameters and RAS/inflammatory markers expression were assessed. Results: the main findings showed that diet-induced obese mice treated with COX-2 inhibitor showed significantly improved glucose and insulin homeostasis, presented decreased body weight gain and the biochemical analyses revealed reduced triglyceride levels and higher serum HDL-c levels as compared to HFD and ST. These results were accompanied by a downregulation of AGT, ACE, TNF-α and IL-6 expression in the group receiving treatment. Conclusion: taken together, these results indicate that ICOX-2 may exhibit therapeutic potential for obesity via the renin-angiotensin system and inflammation.

FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Outra Agência The direct calorimetric analysis is the most effective way to obtain caloric value provided by food. Knowing the amount of energy provided by food is essential for the composition of the individuals' diet. Therefore, this paper aimed to standardize a methodology for quantifying the number of calories present in a fermented milk drink with clove essential oil and in a fermented milk drink. Ten mL of each drink were transferred in to triplicate petri dishes and placed in a forced circulation oven 65 ° C for 24-48 hours to remove moisture to obtain the total solids. These were transferred to a previously tared crucible and inserted into the calorimetric pump until total burning. The results obtained in cal g-1 were converted to Kcal g-1 and finally the amount of Kcal ml-1 of each drink were calculated. The analyzes were submitted to analysis of variance (ANAVA) in a completely randomized design and to the Tukey test was used as means of comparison (p0.05). It can be concluded that the quantification of calories made by this methodology was effective and could later support studies in which it is necessary to calculate with precision the number of calories provided by fermented dairy drinks. A análise calorimétrica direta é forma mais eficaz de se obter o valor calórico fornecido pelo alimento. Conhecer a quantidade de energia fornecida pelo alimento é imprescindível para composição da dieta dos indivíduos. Dessa forma, esse trabalho visou padronizar uma metodologia para quantificação de calorias presentes em uma bebida láctea fermentada adicionada com óleo essencial de cravo da índia e uma bebida láctea fermentada. Dez mL de cada bebida foram transferidos para placas de petri em triplicada e colocadas em estufa de circulação forçada 65°C por 24-48 horas, para remoção da umidade a fim de obter os sólidos totais. Esses foram transferidos para um cadinho previamente tarado e inserido na bomba calorimétrica até queima total. Os resultados obtidos em cal g-1 foram convertidos em Kcal g-1 e por fim calculado a quantidade de Kcal ml-1 de cada bebida. As análises foram submetidas à análise de variância (ANOVA) em delineamento inteiramente ao acaso e ao teste Tukey de comparação de médias (p0,05). Pode-se concluir que a quantificação de calorias feita por essa metodologia foi eficaz e poderá auxiliar posteriormente estudos em que necessite calcular com precisão o número de calorias fornecidas por bebidas lácteas fermentadas.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Objectives: to analyze the mRNA expression of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) in the liver and white adipose tissue samples of individuals with class III obesity (body mass index ≥40.0 kg/m2) with non-alcoholic fatty liver disease (NAFLD). Methods: this cross-sectional study included patients with class III obesity exhibiting early or late morphological presentation of NAFLD (non-alcoholic hepatic steatosis [NAFL], n = 8 and non-alcoholic steatohepatitis [NASH], n = 13, respectively). All patients underwent bariatric surgery and peripheral blood, liver, and visceral white adipose tissue (WAT) samples were collected. Socio-demographic, anthropometric, clinical, plasma biochemical, and nutritional characteristics of each study subject were assessed and compared between patients presenting with NAFL and NASH. IL-6 and TNF-α mRNA expression in the liver and WAT samples were measured by using quantitative real time-polymerase chain reaction (qRT-PCR). Results: individuals with class III obesity and NASH showed higher body mass index (BMI) and higher IL-6 and TNF-α mRNA expression in the WAT compared to that of patients with NAFL (p = 0.01, for all associations). Conclusions: individuals with class III obesity with higher morphological severity of NAFLD exhibited higher BMI and higher IL-6 and TNF-α expression in the WAT. Future prospective studies are warranted to determine how BMI, IL-6, and TNF-α affect the progression of NAFLD in individuals with class III obesity.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Background: the complex pathophysiology of obesity includes low-grade chronic inflammation of white adipose tissue, an increase in plasma levels of pro-inflammatory cytokines as well as genetic factors, which have all emerged as important risk factors. Objective: evaluate the association between the TNFα-308G/A variant and sociodemographic, clinical and behavioral variables in an urban population using overall and central obesity as the measured outcome. Methods: a cross-sectional population-based study was conducted. Anthropometric measures and genotyping were assessed in 808 individuals. The associations were tested using the hierarchical theoretical model and multiple logistic regressions. Results: thirty-one percent of subjects were overweight while 19.4% were obese. No association was observed between genotype frequencies of TNFα-308G/A and either obesity or other variables of adiposity, including waist circumference, waist to height ratio, conicity index, and fat mass. However, age, gender, physical inactivity, and other comorbidities were associated with measures of excess adiposity in the hierarchical model. The phase angle of AA genotype was lower than GA and GG genotypes (p < 0.05). Conclusion: the rs1800629 SNP of the TNFA gene was not associated with the adiposity indicators evaluated in this based population study. However, AA genotype is more likely to have low cellular membrane integrity.

With the present PPL Special Issue on the “Renin-angiotensin system: Role in chronic diseases”, we have attempted to cover some of the chronic diseases associated with key components of RAS, and to address the most important aspects of its functional output. Furthermore, we aimed to include new tendencies and advances, some of them still controversial, but always contemplating what we consider as hot-points for research progress, drug developments and new treatments in a near future. The articles of the Special Issue bring several chronic diseases related to different organs and with various systemic effects.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais Outra Agência Different factors may contribute to the development of neurodegenerative diseases. Among them, metabolic syndrome (MS), which has reached epidemic proportions, has emerged as a potential element that may be involved in neurodegeneration. Furthermore, studies have shown the importance of the sirtuin family in neuronal survival and MS, which opens the possibility of new pharmacological targets. This study investigates the influence of sirtuin metabolic pathways by examining the functional capacities of glucose-induced obesity in an excitotoxic state induced by a quinolinic acid (QA) animal model. Mice were divided into two groups that received different diets for 8 weeks: one group received a regular diet, and the other group received a high-fat diet (HF) to induce MS. The animals were submitted to a stereotaxic surgery and subdivided into four groups: Standard (ST), Standard-QA (ST-QA), HF and HF-QA. The QA groups were given a 250 nL quinolinic acid injection in the right striatum and PBS was injected in the other groups. Obese mice presented with a weight gain of 40 % more than the ST group beyond acquiring an insulin resistance. QA induced motor impairment and neurodegeneration in both ST-QA and HF-QA, although no difference was observed between these groups. The HF-QA group showed a reduction in adiposity when compared with the groups that received PBS. Therefore, the HF-QA group demonstrated a commitment-dependent metabolic pathway. The results suggest that an obesogenic diet does not aggravate the neurodegeneration induced by QA. However, the excitotoxicity induced by QA promotes a sirtuin pathway impairment that contributes to metabolic changes.

CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Introdução: Mudanças no estilo de vida da sociedade, especialmente o aumento do consumo de alimentos ultra processados, alta ingestão de carne vermelha, açúcar e sal e escassez de fibras alimentares possuem implicações para a microbiota intestinal coevoluída além de aumentar a incidência de adiposidade e doenças inflamatórias crônicas. A fibra alimentar consiste em formas não digeríveis de carboidratos, geralmente como polissacarídeos que se originam de alimentos à base de plantas. Dentre as fibras, a inulina tem sido muito estudada com ênfase na regulação do peso e na melhoria de parâmetros metabólicos, e associada a efeitos positivos no metabolismo lipídico do hospedeiro proporcionando melhorias na homeostase lipídica, diminuição das taxas séricas de colesterol e triglicerídeos, redução da lipogênese hepática com impactos positivos na saciedade e no peso corporal. Objetivos: Avaliar a influência de uma suplementação com o prebiótico inulina no metabolismo de camundongos. Métodos: Camundongos machos Swiss foram alimentados por 4 semanas com 2 dietas isocalóricas diferentes: Standard (ST), Standard + Inulin (ST+I, 10%). Foram mensurados parâmetros como ingestão de alimentos/energia e composição corporal, realizou-se teste de sensibilidade a insulina e tolerância a glicose. Os tecidos adiposos epidídimal, retroperitoneal, mesentérico, subcutâneo e marrom, além do fígado, músculo, estômago, intestino grosso e delgado foram pesados; destes o fígado, tecido adiposo epididimal, músculo, estômago, intestino grosso e delgado foram armazenados a -80 oC para posterior análise molecular. Foram também avaliados os seguintes parâmetros bioquímicos: colesterol total (TC), lipoproteína de alta densidade (HDL), triglicerídeos (TG), transaminases alaninas (ALT/GPT) e transferência de aspartato (AST/GOT) utilizando kits enzimáticos (Wiener Laboratories, Rosario, Argentina), histologia e expressão de mRNA do tecido adiposo epididimal. Resultados: A suplementação dietética foi benéfica tendo em vista que promoveu um aumento nos índices bioquímicos do HDL, diminuiu as enzimas GPT relacionadas ao risco de lesão hepática e melhorou o perfil glicêmico ao aumentar a sensibilidade à insulina. Ainda, reduziu a expressão do gene da proteína transmembrana Toll-like receptor 4 (TLR4) e a interleucina 6 (IL6), na avaliação da expressão gênica de marcadores de adipócitos “bege” (Pgc1α, Ucp1, Cidea). Foi também observada uma tendência de aumento desses genes no grupo tratado com inulina em relação ao grupo controle no tecido adiposo epididimal, e uma diminuição da hipertrofia dos adipócitos com um predomínio de pequenos adipócitos do grupo tratado com inulina em comparação ao grupo controle enquanto os adipócitos pequenos estão relacionados a um risco diminuído de distúrbios no metabolismo. Nos adipócitos hipertróficos ocorreu um aumento da secreção de citocinas inflamatórias e diminuição da secreção de adipocinas anti-inflamatórias. Conclusão: A suplementação com inulina pode melhorar os índices relacionados ao surgimento da obesidade como inflamação crônica, previnir a disfunção da matriz extracelular (MEC) que induzem mudanças na funcionalidade do tecido adiposo e variações em seu perfil de secreção de adipocinas indicando a inulina como uma alternativa natural anti-obesidade. Introduction: Changes in the society’s lifestyle, especially the increase in the consumption of ultra-processed foods, the high intake of red meat, sugar and salt and the scarcity of dietary fibers have implications for the gut microbiota with increasing incidence of adiposity and chronic inflammatory diseases. Dietary fiber are non-digestible forms of carbohydrates and polysaccharides that originate from plant-based foods. Among fibers inulin has been widely studied with emphasis in the area of weight regulation and improvement of metabolic parameters, and linked to positive effects on the host lipid metabolism providing improvements in lipid homeotase, reduction of serum cholesterol and triglyceride rates, reduction of lipogenesis with positive impacts on satiety and body weight. Objectives: To investigate the effects of prebiotic inulin supplementation on the metabolism of mice. Methods: Male Swiss mice were fed for 4 weeks with 2 different isocaloric diets: Standard (ST), Standard + Inulin (ST+I, 10%). Measurements of some parameters, e.g. food/energy intake, body composition data, insulin sensitivity and glucose tolerance. Epidimal adipose, retroperitoneal, mesenteric, subcutaneous and brown tissues, in addition to the liver, muscle, stomach, large and small intestine were weighed; among them, liver, epididimal adipose tissue, muscle, stomach, and the large and small intestines were stored at -80 ˚C for further molecular analysis. In addition, analyses were undertaken for the evaluation of the following parameters total cholesterol (TC), high density lipoprotein (HDL), triglycerides (TG), alanine transaminases (ALT/GPT) and aspartate transfer (AST/GOT) using enzyme kits (Wiener Laboratories, Rosario, Argentina), histology and mRNA expression of epididymal adipose tissue were analyzed. Results: The dietary supplementation of inulin was benefic as it increased HDL biochemical indices, decreased GPT enzymes related to the risk of liver injury, improved the glycemic profile and increased insulin sensitivity. It also reduced the expression of the Toll-like receptor 4 transmembrane protein (TLR4) and interleukin 6 (IL6) in the evaluation of the gene expression of beige adipocytes markers (Pgc1α, Ucp1, Cidea). There was also a trend in the increase in these genes of the treated group compared to the control regarding epididymal adipose tissue, and a decreased hypertrophy of adipocytes with a predominance of small adipocytes while small adipocytes are related to a decreased risk of disorders in metabolism . In hypertrophic adipocytes, there was an increased secretion of inflammatory cytokines and decreased secretion of anti-inflammatory adipocins. Conclusion: Inulin supplementation may improve rates related to the onset of obesity as inflammation prevents extracellular matrix dysfunction (ECM) that induce changes in adipose tissue functionality and variations in its adipokine secretion profile indicating inulin as a natural anti-obesity alternative.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico A Diabetes mellitus (DM) é uma das doenças crônicas mais documentadas no mundo e afeta mais de 100 milhões de pessoas no planeta. Possui como característica principal a hiperglicemia crônica, resultante da ausência da produção de insulina ou à resistência da mesma, a diabetes mellitus tipo 2 é o tipo mais prevalente, representando cerca de 85-90% dos casos. O controle inadequado da diabetes compromete tecidos musculares e nervosos, cujo metabolismo depende fundamentalmente do suprimento de glicose e aumenta a probabilidade do surgimento de complicações microvasculares, como: retinopatia diabética, nefropatia diabética, neuropatia autonômica e neuropatia diabética periférica. As neuropatias diabéticas caracterizam-se pela presença de sintomas e/ou sinais de disfunção dos nervos do sistema nervoso periférico somático e/ou do autonômico em indivíduos com diagnóstico de DM. Atualmente existe um número reduzido de tratamentos disponíveis para a dor neuropática diabética, sendo basicamente utilizados antidepressivos tricíclicos e anticonvulsivantes, no entanto tais fármacos não possuem grande eficácia no controle da dor, com apenas 30% dos pacientes apresentando algum tipo de alívio. Neste contexto, a proposta deste estudo foi avaliar se a via PI3Kγ/AKT/NO/GMPc/canais para potássios sensíveis ao ATP, participa do controle endógeno na dor neuropática diabética. A descoberta de vias que participem de mecanismos modulatórios da dor podem trazer respostas importantes para a escolha de fármacos mais eficazes ou a criação de drogas específicas que garantam alívio satisfatório deste tipo de dor, com consequente melhoria da qualidade de vida dos pacientes. A dor neuropática diabética foi induzida por dieta hiperlipídica (HFD 40%), os animais foram alimentados por 12 semanas até o surgimento da hiperalgesia, este fenômeno foi então acompanhado do diagnóstico de obesidade, resistência a insulina e intolerância a glicose, representando assim um modelo semelhante a diabetes tipo 2 em humanos. A hiperalgesia foi testada através do método de compressão mecânica da pata e para confirmar que a dor frente ao estímulo mecânico possui características neuropáticas e não apenas inflamatórias, realizou-se a histopatologia da pata e do nervo ciático dos animais do grupo controle e alimentados com a dieta diabetogênica. Os resultados encontrados foram satisfatórios para a comprovação de que a dor evocada pela dieta possui características tipicamente neuropática, registros de desorganização do tecido conjuntivo do epineuro/perineuro, axônios retraídos e posicionados excentricamente, aumento do espaço correspondente à mielina e perda axonal foram observados, garantindo assim a eficácia do modelo na indução da dor neuropática diabética. Para os testes farmacológicos, as análises estatísticas utilizaram two-way ANOVA, seguido do pós-teste de Bonferroni, para a quantificação das alterações morfológicas por análise histopatológica e imunohistoquímica, utilizou-se teste T pareado. Todas as drogas foram administradas pela via intraplantar. Para a avaliação da participação da via PI3k, foi utilizado AS-605240, inibidor seletivo de PI3Kγ nas dosagens de 90 e 180 µg/pata, observou-se que PI3Kγ quando inibida não modulou a nocicepção induzida pela dieta hiperlipídica. Para a determinação da expressão das proteínas p-AKT/total AKT, utilizou-se a técnica de Western Blot e para isso foram coletados coxins plantares dos animais do grupo controle e alimentados com a dieta diabetogênica. Verificou-se diferença estatística significativa na expressão da proteína p-AKT, que representa a forma ativa desta proteína, a mesma, encontra-se expressa em menor quantidade nos animais acometidos pela dor neuropática diabética (DNP), o que reforça a não participação desta via na modulação endógena na dor investigada. Para avaliação da participação da via de sinalização do óxido nítrico foram utilizadas as drogas L-NOarg, inibidor não seletivo das enzimas oxido nítrico sintase, nas doses de 24 e 48 µg/pata e o ODQ, inibidor seletivo da enzima guanilato ciclase solúvel, nas doses de 100 e 200 µg/pata, não se observou modulação endógena na dor neuropática diabética quando utilizado, L-NOarg ou ODQ, significando que a via do óxido nítrico não participa da modulação endógena da dor investigada. Seguimos para a análise da participação seletiva destes canais, desta forma, foi utilizada a glibenclamida, bloqueador seletivo de canais para potássio sensíveis ao ATP, nas doses 80 e 160 µg/pata, onde observou-se redução do limiar nociceptivo nos animais com dor neuropática diabética, o que significa que estes canais participam endogenamente na tentativa de controle da dor neuropática diabética. Após esses achados, investigou-a expressão dos canais para potássio sensíveis ao ATP, com intuito de observar se, em um cenário de DNP induzido exclusivamente por dieta rica em gordura, estes apresentavam sua expressão alterada, para isso, foi realizada a imunohistoquimica dos coxins plantares, estes foram marcados com Kir 6.2, um marcador de canais para potássio sensíveis ao ATP e os resultados encontrados, apresentaram aumento da expressão destes canais, o que acredita-se ser uma estratégia de alteração funcional do sistema endógeno, na tentativa de controle da dor. Para determinação da atividade de canais para potássio sensíveis a voltagem (KV), foi utilizado o Tetraetilamonio, bloqueador seletivo de canais para KV, na dose de 30 µg, onde observou-se modulação do limiar nociceptivo dos animais acometidos pela dor neuropática diabética. A partir destes achados, investigou-se também a participação dos canais para potássio sensíveis ao cálcio de baixa e alta condutância. Para tais análises utilizou-se respectivamente, Dequalíneo (bloqueador seletivo de canais para potássio sensíveis ao cálcio de baixa condutância), na dose de 50 µg/pata e Paxilína (bloqueador seletivo de canais para potássio sensíveis ao cálcio de alta condutância), na dose de 20 µg/pata. O limiar nociceptivo dos animais com dor neuropática diabética não sofreu alteração quando administrado nenhum dos fármacos supracitados, descartando assim a participação dos canais para potássio sensíveis ao cálcio na modulação endógena da dor neuropática diabética. Os resultados fornecem evidências de que a dor evocada pelo modelo de indução exclusivamente por dieta hiperlipídica possui característica neuropática. Além disso, observou-se que a via PI3Kγ/AKT/NO/GMPc não participa endogenamente do controle da dor neuropática diabética, no entanto, os canais para potássio sensíveis ao ATP e a voltagem, modulam endogenamente a dor supracitada, o bloqueio destes canais reduziu o limiar nociceptivo dos animais acometidos pela dor, além disso, a expressão de KATP encontra-se aumentada. Nossa hipótese é que o aumento da expressão destes canais sejam uma adaptação fisiológica funcional do sistema endógeno periférico, uma tentativa de controle da dor neuropática diabética e que fármacos que potencializem a abertura destes canais podem contribuir com o controle da dor neuropática diabética. APOIO FINANCEIRO: CAPES. PROTOCOLO CEUA: 57/2017. APOIO FINANCEIRO: CAPES. PROTOCOLO CEUA: 57/2017. PEREIRA, William Valadares Campos. Investigation of the participation of the pi3kγ / akt / no / gmpc / atp-sensitive potassium channels in the endogenous control of neuropathic pain induced by a high-fat diet in obese mice.2021. 86 páginas. Universidade Federal de Minas Gerais Instituto de Ciências Biológicas Programa de Pós-graduação em Ciências Biológicas - Fisiologia e Farmacologia. Diabetes mellitus (DM) is one of the most documented chronic diseases in the world and affects more than 100 million people on the planet. Its main characteristic is chronic hyperglycemia, resulting from the absence of insulin production or its resistance, type 2 diabetes mellitus is the most prevalent type, representing about 85-90% of cases. Inadequate diabetes control compromises muscle and nerve tissues, the metabolism of which depends fundamentally on the supply of glucose and increases the likelihood of the appearance of microvascular complications, such as: diabetic retinopathy, diabetic nephropathy, autonomic neuropathy and peripheral diabetic neuropathy. Diabetic neuropathies are characterized by the presence of symptoms and / or signs of somatic and / or autonomic nervous system nerve dysfunction in individuals diagnosed with DM. Currently, there is a reduced number of treatments available for diabetic neuropathic pain, and basically tricyclic antidepressants and anticonvulsants are used, however, these drugs are not very effective in controlling pain, with only 30% of patients showing some type of relief. In this context, the purpose of this study was to evaluate whether the PI3Kγ / AKT / NO / cGMP / channels for potassium sensitive to ATP, participates in endogenous control in diabetic neuropathic pain. The discovery of pathways that participate in modulatory mechanisms of pain can bring important answers to the choice of more effective drugs or the creation of specific drugs that guarantee satisfactory relief of this type of pain, with a consequent improvement in the quality of life of patients. Diabetic neuropathic pain was induced by a high-fat diet (HFD 40%), the animals were fed for 12 weeks until the onset of hyperalgesia, this phenomenon was then accompanied by the diagnosis of obesity, insulin resistance and glucose intolerance, thus representing a model similar to type 2 diabetes in humans. Hyperalgesia was tested using the mechanical paw compression method and to confirm that the pain at the mechanical stimulus has neuropathic and not just inflammatory characteristics, the histopathology of the paw and the sciatic nerve of the animals in the control group and fed with diabetogenic diet. The results found were satisfactory to prove that the pain evoked by the diet has typical neuropathic characteristics, records of disorganization of the connective tissue of the epineurium / perineurium, axons retracted and positioned eccentrically, an increase in the space corresponding to myelin and axonal loss were observed, guaranteeing thus the effectiveness of the model in the induction of diabetic neuropathic pain. For pharmacological tests, statistical analyzes used two-way ANOVA, followed by the Bonferroni post-test, for the quantification of morphological changes by histopathological and immunohistochemical analysis, a paired T test was used. All drugs were administered via the intraplantar route. To assess the participation of the PI3k pathway, AS-605240 was used, a selective inhibitor of PI3Kγ in the dosages of 90 and 180 µg / paw, it was observed that PI3Kγ when inhibited did not modulate the nociception induced by the hyperlipidic diet. For the determination of the expression of p-AKT / total AKT proteins, the Western blot technique was used and for this purpose plantar cushions were collected from the animals of the control group and fed with the diabetogenic diet. There was a statistically significant difference in the expression of the p-AKT protein, which represents the active form of this protein, the same, it is expressed in a smaller amount in animals affected by diabetic neuropathic pain (DNP), which reinforces the non-participation of this via endogenous modulation in the investigated pain. To evaluate the participation of the nitric oxide signaling pathway, the drugs L-NOarg, a non-selective inhibitor of the enzymes nitric oxide synthase, were used at doses of 24 and 48 µg / paw and ODQ, a selective inhibitor of the enzyme soluble guanylate cyclase, in doses of 100 and 200 µg / paw, endogenous modulation was not observed in diabetic neuropathic pain when used, L-NOarg or ODQ, meaning that the nitric oxide pathway does not participate in the endogenous modulation of the investigated pain. We proceeded to the analysis of the selective participation of these channels, thus, we used glibenclamide, a selective blocker of potassium channels sensitive to ATP, at doses 80 and 160 µg / paw, where a reduction in the nociceptive threshold was observed in animals with neuropathic pain diabetic, which means that these channels participate endogenously in the attempt to control diabetic neuropathic pain. After these findings, he investigated the expression of ATP-sensitive potassium channels, with the aim of observing whether, in a scenario of DNP induced exclusively by a high-fat diet, they showed their altered expression, for this, immunohistochemistry of the cushions was performed. plants, these were marked with Kir 6.2, a marker of potassium channels sensitive to ATP and the results found, showed an increase in the expression of these channels, which is believed to be a strategy of functional alteration of the endogenous system, in an attempt to control the ache. To determine the activity of voltage-sensitive potassium channels (KV), Tetraethylammonium, a selective blocker of channels for KV, was used at a dose of 30 µg, where modulation of the nociceptive threshold of animals affected by diabetic neuropathic pain was observed. Based on these findings, the participation of low- and high-conductivity calcium channels for potassium was also investigated. For such analyzes, Dequalíneo (selective blocker of potassium channels sensitive to calcium of low conductance) was used, respectively, in the dose of 50 µg / paw and Paxilína (selective blocker of channels for potassium sensitive to calcium of high conductance), in the dose 20 µg / paw. The nociceptive threshold of animals with diabetic neuropathic pain did not change when any of the aforementioned drugs were administered, thus ruling out the participation of calcium-sensitive potassium channels in the endogenous modulation of diabetic neuropathic pain. The results provide evidence that the pain evoked by the induction model exclusively by high-fat diet has a neuropathic characteristic. In addition, it was observed that the PI3Kγ / AKT / NO / cGMP pathway does not participate endogenously in the control of diabetic neuropathic pain, however, the ATP-sensitive potassium channels and voltage, endogenously modulate the pain, blocking these channels reduced the nociceptive threshold of animals affected by pain, in addition, the expression of KATP is increased. Our hypothesis is that the increased expression of these channels is a functional physiological adaptation of the peripheral endogenous system, an attempt to control diabetic neuropathic pain and that drugs that enhance the opening of these channels can contribute to the control of diabetic neuropathic pain. FINANCIAL SUPPORT: CAPES. CEUA PROTOCOL: 57/2017.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico A Alamandina é um heptapeptídeo que faz parte do Sistema Renina-Angiotensina (SRA). A sequência de aminoácidos da alamandina se difere da sequência de aminoácidos da Ang-(1-7) apenas pela presença de alanina no lugar do aspartato. Além da estrutura, os dois peptídeos compartilham semelhanças entre seus efeitos. Entretanto, os efeitos da alamandina são mediados pelo receptor MrgD. Este receptor é expresso em diferentes tecidos tais como, artéria, cerebelo, coração e tecido adiposo. Os outros receptores do SRA (MAS, AT1R e AT2R) também são expressos em diversos órgãos, inclusive em tecidos adiposos branco e marrom. Essa expressão localizada em tecidos endócrinos proporciona grande influência do SRA ao metabolismo. No tecido adiposo marrom (TAM) a ativação do eixo ECA2/Ang-(1-7) promove aumento de gasto energético e da atividade de diversos marcadores como AMPK, UCP1 e PGC1a. Os nossos primeiros resultados nos indicaram que o receptor MrgD também pode ter influência sobre o TAM, pois observamos que os animais MrgD/KO possuem o TAM extremamente diminuído e que animais C57BL6/J obesos apresentam expressão diminuída de MrgD no TAM. Não à toa este tecido e este receptor nos chamou a atenção. Uma vez que, não temos estudos a respeito do efeito do eixo Alamandina/MrgD sobre o metabolismo, uma técnica que promova resultados abrangentes fornece dicas de focos de estudo, assim como diferentes linhas de trabalhos futuros. Neste sentido, a técnica de sequenciamento de RNA, para RNA extraído de TAM de animais MrgD/KO obesos e magros, foi utilizada. A obesidade foi induzida por uma dieta rica em glicose (HG) pelo período de 8 semanas. A expressão do receptor MrgD é essencial para uma resposta à dieta HG, visto que os animais MrgD/KO HG deixaram de regular mais de 1000 genes em comparação ao grupo MrgD/KO ST. Na ausência do receptor MrgD o TAM é regulado negativamente, diminuindo a expressão de mais 400 transcritos. Os animais MrgD/KO diminuem a expressão de marcadores termogênicos e aumentam a expressão de marcadores de fibrose na comparação entre MrgD/KO HG vs WT HG. Além disso, a ausência do receptor MrgD promove uma tendência para alteração em diversas vias tais quais, sinalização de cálcio, cadeia transportadora de elétrons, termogênese, cardiomiopatias, entre outras. De acordo com as análises encontramos alguns dos principais alvos do eixo alamandina/MrgD: AMPK, canais iônicos e componentes da matriz extracelular. Alamandine is a heptapeptide part of the renin-angiotensin system (RAS). The amino acid sequence of alamandine (Ala-Arg-Val-Tyr-Ile-His-Pro) is similar to the amino acid sequence of ANG-(1-7) (Asp-Arg-Val-Tyr-Ile-His-Pro), except for the presence of alanine in the place of aspartate. In addition to the structure, the effects of alamandine are also similar to the effects of Ang-(1-7). Despite the similarities, the effects of alamandine are mediated by the MrgD receptor. The MrgD receptor is expressed in a variety of tissues e.g. dorsal root ganglia, artery, bladder, cerebellum, heart, and adipose tissue. The other RAS receptors (MAS, AT1R and AT2R) are also expressed in a wide variety of organs, including white and brown adipose tissues. This localized expression in endocrine tissues provides a great influence of the RAS on the metabolism. In the brown adipose tissue (BAT), the ECA2/Ang-(1-7) axis activity promotes increased energy expenditure and activity of several markers such as AMPK, UCP1 and PGC1a. Our first results indicated that the alamandine receptor, MrgD, may also have an influence on BAT, as we observed that MrgD/KO animals have extremely decreased BAT and obese C57BL6/J mice show decreased expression of MrgD in BAT. Therefore, this tissue and this receptor caught our attention. Since we have no studies on the effect of the alamandina/MrgD axis on metabolism, a technique that promotes comprehensive results allows for a better north and can provide different lines for future work. In this sense, the RNA sequencing technique for RNA extracted from BAT of obese and lean MrgD/KO mice was performed. Obesity was induced by a high-glucose diet (HG) for 8 weeks. Obesity induced transcriptional changes in the BAT of WT HG animals related to increased metabolism and adaptive thermogenesis. The expression of the MrgD receptor is essential for a HG diet response, since the MrgD/KO HG group failed in regulating more than 1000 genes compared to the MrgD/KO ST group. In the absence of the MrgD receptor BAT transcripts are deeply downregulated decreasing the expression of over 400 genes. MrgD/KO animals decreased the expression of thermogenic markers and increased the expression of fibrosis markers in the comparison between MrgD/KO HG vs WT HG. In addition, the absence of the MrgD receptor promotes a tendency to regulate several pathways e.g., calcium signaling, electron transport chain, thermogenesis, and cardiomyopathies. According to the analysis we found some of the main targets of the alamandin/MrgD axis: AMPK, ion channels and components of the extracellular matrix.

O óleo essencial de cravo-da-índia apresenta atividade antimicrobiana, antioxidante, anticâncer entre outras. Estudos prévios analisaram o potencial do cravo-da-índia como substituto ao conservante sintético sorbato de potássio em bebida láctea fermentada. Sendo assim, neste trabalho verificou-se in sílico, in vitro e in vivo, o potencial antioxidante da bebida láctea com óleo essencial de cravo-da-índia e os impactos da ingestão dessa bebida para o organismo. Foram produzidas bebidas lácteas fermentadas com óleo essencial de cravo-da-índia (2 ul/ml), bebidas sem conservantes e com conservante sintético (sorbato de potássio). Análises previstas na legislação foram realizadas, como as físico-químicas de teor de gordura, proteína e acidez, testes microbiológicos e análise de calorimetria. Para avaliar a atividade antioxidante foram realizadas análises de DPPH e CE50. Análise de headspace foi realizada para identificação de compostos envolvidos nessa ação. Lâminas histopatológica utilizando tecido adiposo de camundongos machos swiss e análises de atividade antioxidante in vivo como avaliação das enzimas antioxidantes e quantificação por PCR em tempo real das enzimas superóxido dismutase (SOD), catalase (CAT) e glutationa peroxidase (GPx). Os resultados demonstram que as bebidas lácteas produzidas atenderam os parâmetros físico-químicos para proteína (2,06g de proteína/100g) e acidez (0,75 a 0,88%). Para gordura (0,84g de gordura/100g), obteve-se resultados considerados para bebida láctea parcialmente desnatada. As análises microbiológicas apresentaram resultados negativos para Salmonella sp., coliformes totais e coliformes termotolerantes e valores maiores que 10-6 UFC/mL de bactérias lácteas durante o período de estocagem de 14 dias. Nas análises de atividade antioxidante in vitro a bebida láctea com óleo essencial apresentou atividade antioxidante com valores de 82,7 a 93,4%, em relação à bebida com sorbato de potássio (5,60 a 44,8%) e a bebida sem conservantes (4,86 a 42,3%). Os resultados da concentração efetiva (CE50) mostraram maior capacidade da bebida com o óleo em seqüestrar radicais livres utilizando menor concentração do que o antioxidante convencional Butil hidroxitolueno (BHT). O eugenol foi detectado nas análises de headspace da bebida, sendo este composto um dos responsáveis pela atividade antioxidante do óleo. O grupo que recebeu a bebida láctea com o óleo essencial apresentou menor quantidade de enzimas antioxidantes expressas e menor área dos adipócitos em relação aos outros grupos experimentais. Deste modo o óleo essencial de cravo-da-índia é um potencial substituto aos conservantes sintéticos, apresentam atividade antioxidante comprovada in vitro e in vivo e não apresentou alterações histológicas no tecido adiposo após a ingestão. Clove essential oil has antimicrobial, antioxidant, anticancer activity among others. Previous studies have looked at the potential of clove as a substitute for the synthetic preservative potassium sorbate in fermented dairy beverage. Thus, in this work it was verified in sílico, in vitro and in vivo, the antioxidant potential of the milk drink with clove essential oil and the impacts of the intake of this drink for the organism. Fermented dairy beverage with clove essential oil (2 µl/ml), preservative-free beverages and synthetic preservative (potassium sorbate) were produced. Analyzes provided for in the legislation were performed, such as physicochemical of fat content, protein and acidity, microbiological tests and calorimetry analysis. To evaluate antioxidant activity, DPPH and EC50 analyzes were performed. Headspace analysis was performed to identify compounds involved in this action. Histopathological slides using adipose tissue from swiss male mice and in vivo antioxidant activity analyzes as evaluation of antioxidant enzymes and real time PCR quantification of the enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). The results show that the dairy drinks produced met the physicochemical parameters for protein (2.06g protein / 100g) and acidity (0.75 to 0.88%). For fat (0.84g fat / 100g) results were obtained for partially skimmed milk drink. Microbiological analyzes showed negative results for Salmonella sp., Total coliforms and thermotolerant coliforms and values greater than 10-6 CFU / mL of dairy bacteria during the 14 days storage period. In the in vitro antioxidant activity analyzes the essential oil fermented dairy beverage presented antioxidant activity with values of 82.7 to 93.4%, compared to the potassium sorbate drink (5.60 to 44.8%) and the preservativefree drink (4.86 to 42.3%). The results of the effective concentration (EC50) showed greater ability of the drink with the oil to sequester free radicals using lower concentration than the conventional antioxidant butylated hydroxytoluene (BHT). Eugenol was detected in the headspace analysis of the drink, being this compound responsible for the antioxidant activity of the oil. The group that received the milk drink with the essential oil presented less amount of expressed antioxidant enzymes and smaller area of adipocytes in relation to the other experimental groups. As such, clove essential oil is a potential substitute for synthetic preservatives, has proven in vitro and in vivo antioxidant activity and showed no histological changes in adipose tissue after ingestion.