The effects of polyphenol-rich extracts on obesity-linked metabolic diseases

Tableau d'honneur de la FÉSPL'obésité et son large spectre de maladies associées ont atteint des proportions pandémiques inquiétantes, soulignant la nécessité d’identifier des stratégies alternatives afin de lutter contre ce problème. À ce titre, les régimes riches en fruits et légumes représentent des déterminants bien établis d'une incidence plus faible de ces désordres métabolique. Grandement soutenus par des évidences épidémiologiques reliant les régimes riches en polyphénols et un meilleur état de santé, des efforts considérables ont été déployés afin d’étudier les bienfaits de ces métabolites secondaires des plantes. Malgré tout, les mécanismes par lesquels ces phytoéléments améliorent la santé métabolique demeurent encore mal compris, ce qui en justifie une étude plus approfondie. D’autre part, de plus en plus d’évidences indiquent que les bactéries intestinales exercent un important contrôle sur des aspects clés du métabolisme, et on comprend aujourd’hui que plusieurs phytoéléments de baies ont une biodisponibilité limitée, atteignant ainsi le colon qui abrite la plus vaste part du microbiote intestinal. Le travail présenté dans cette thèse vise donc à étudier l’impact de phytoéléments de baies sur le syndrome métabolique de souris soumises à une diète obèsogène et d’en comprendre le rôle du microbiote intestinal dans ces effets. En traitant quotidiennement ces animaux avec des extraits riches en polyphénols d'une gamme de baies aux compositions polyphénoliques variées, nous avons montré que les extraits les plus bioactifs (c.- à-d., canneberge, cloudberry, alpine bearberry, lingonberry et camu camu) partagent la capacité de diminuer l'inflammation intestinale, l’entotoxémie métabolique, la stéatose hépatique et la résistance à l'insuline. L'analyse des populations microbiennes fécales par séquençage du gène 16S ARNr a révélé que l'état métabolique amélioré lié à l'administration de ces extraits était associé à un remodelage draconien du microbiote intestinal, marqué par une expansion d'Akkermansia muciniphila. Cette bactérie intestinale est fortement associée à un faible niveau d’adiposité chez l’humain et son administration à des souris obèses a été montrée suffisante pour renverser le syndrome métabolique. Par ailleurs, les résultats présentés dans cette thèse suggèrent que les polymères de polyphénols, à savoir les proanthocyanidines et les ellagitannins, pourraient bien être des iv molécules clés dans les effets bénéfiques observés, ouvrant la voie à plus de recherche en ce sens. L’ingestion régulière de ces polyphénols par la consommation de canneberges, de cloudberry, d'alpine bearberry, de lingonberry et de camu camu représentent donc une stratégie efficace pour la prévention de désordres métaboliques associés à l’obésité. Cet ouvrage ouvre ainsi à de nouveaux concepts mécanistiques, ciblant l’axe intestin-foie et le microbiote intestinal pour expliquer les effets bénéfiques des polyphénols sur la santé métabolique.Obesity and its wide spectrum of associated diseases have reached worrisome pandemic proportions, underscoring the need for alternative strategies to fight this problem. Plant-rich diets are well-established determinants of a lower incidence of obesity-related diseases, and fruits are important components of these diets. Supported by strong epidemiological evidence linking polyphenol-rich diets and better health status, research has been focused on the potential health effects of these plant secondary metabolites, albeit the mechanisms by which these poorly bioavailable phytonutrients improve metabolic health remains are not yet fully understood. Since there is compelling evidence for a relationship between host metabolic control and the gut microbiota, the work presented in this thesis aimed to investigate the impact of polyphenol-rich berry extracts on features of the metabolic syndrome in diet-induced obese mice. The work presented in this thesis also focuses on the relationship between putative gut microbial alterations driven by dietary polyphenols and its relevance to host metabolism. By daily treating dietinduced obese mice with polyphenol-rich extracts of a wide range of berries (with varied polyphenolic concentration and composition) we demonstrated that the most bioactive extracts (i.e., cranberry, cloudberry, alpine bearberry, lingonberry and camu camu) shared in common the ability to dampen intestinal inflammation and bacterial lipopolysaccharide leakage to systemic circulation, findings associated with reduced hepatic steatosis and improved insulin resistance. 16S rRNA genebased analysis of fecal DNA revealed that the improved metabolic status linked to the administration of these polyphenolic extracts was associated with a drastic gut microbial remodeling, marked by a consistent bloom of Akkermansia muciniphila. This gut bacterium is strongly associated with leanness in humans and its administration to obese mice reversed features of the metabolic syndrome. The findings presented in this thesis suggest that polymers of polyphenols, namely proanthocyanidins and ellagitannins, may have a superior impact on the gut-liver homeostasis, supporting further research on these particular classes of phenolic phytonutrients. While bringing evidence that substantiate the regular consumption of sources of proanthocyanidins and ellagitannins as a strategy to prevent prevalent chronic diseases associated with obesity, this work provides novel mechanistic insights pointing to the gut-liver axis and the gut microbiota as primary targets of dietary polyphenols in order to improve metabolic health

Rethinking paradigms for studying mechanisms of action of plant bioactives

Many foods in our diets such as berries, tea, chocolate and wine contain flavonoids, which are natural components of plants. A substantial body of evidence supports the role of flavonoids in providing protection against cardio-metabolic diseases and disorders. Despite the nearly exponential growth in flavonoid research in the past 20 years, limited progress has been made in understanding how these dietary components work. Research initially focused on their antioxidant activity without taking into account their metabolism, which now appears extensive. This has provided a new research impetus to understand the biological activity of the flavonoid metabolites. Here, we outline recent research, which suggests a highly complex interplay between metabolism, intestinal microflora, the immune system and various tissues of our body

O ciberativismo como ferramenta de grandes mobilizações humanas: das revoltas no Oriente Médio às ações pacíficas do Greenpeace no Brasil

O presente texto aborda a utilização das infovias da informação como ferramentas para grandes mobilizações humanas, que deram origem às revoltas populares em países do Oriente Médio. Aborda os conceitos que definem o ciberativismo e sua utilização por movimentos civis organizados em tempos de revoluções e também de paz, na defesa dos Direitos Humanos, como aconteceu no caso da iraniana Sakineh Ahstiani, condenada à morte por apedrejamento. Dedica-se especialmente ao estudo de caso do ciberativismo no Brasil, a partir do Greenpeac

Avaliação do efeito tóxico de preservantes de bambu sobre a germinação e crescimento de Lactuca sativa

Materials such as wood and bamboo in their various applications are subject to degradation by deteriorating organisms like fungi and insects. Chemical treatments are routinely used by bamboo professionals aiming to control this degradation. However, it is usual the dispose of these used solutions on soil and the environmental risks and effects on vegetation of this improper disposal are still unknown. Thus, this study aims to evaluate the phytotoxicity of CCB solutions (compound based on copper, chromium and boron), tetrahydrate sodium octaborate and CB (copper sulfate with boric acid) under different concentrations in the germination and development of lettuce (Lactuca sativa). The pH and electrical conductivity of the prepared solutions were also measured. The results show that the three preservatives are phytotoxic and inhibit root development, even after dilutions of 50 times that used by professionals. Thus, the disposal of these effluents in the soil or water bodies may have negative environmental impacts on vegetation, requiring treatment after use on preservation of the culms or higher dilutions of the effluents before the disposal.Materiais como madeiras e bambu em suas diversas aplicações estão sujeitos à degradação por organismos deteriorantes como fungos e insetos. Dessa forma, tratamentos químicos são rotineiramente utilizados por profissionais de bambu para controlar essa degradação. No entanto, é usual o descarte dessas soluções no solo após o uso e os riscos ambientais e efeitos sobre à vegetação desse descarte indevido ainda são desconhecidos. Assim, esse estudo visa avaliar a fitotoxicidade de soluções de CCB (composto baseado em cobre, cromo e boro), de Octaborato de sódio tetraidratado e de CB (sulfato de cobre com ácido bórico) sob diferentes concentrações na germinação e desenvolvimento de alface (Lactuca sativa). Foram também medidos os valores de pH e condutividade elétrica das soluções preparadas. Os resultados mostram que os três preservantes são fitotóxicos e inibem o desenvolvimento da radícula, mesmo após diluições de 50 vezes a utilizada pelos profissionais. Dessa forma, o descarte desses efluentes no solo ou em corpos d’água pode acarretar impactos ambientais negativos à vegetação, necessitando de tratamento posterior ao uso na preservação dos colmos ou maiores diluições do efluente antes do lançamento

Eficiência do sistema de lodos ativados de uma indústria de equipamentos elétricos

Liquid effluent generation in industrial plants is associated with production processes and employees. Based on the current legislation, these effluents must be subjected to treatment processes in order to be discharged at acceptable levels in receiving waterbodies. The company evaluated in the current study manufactures household and industrial tools and instruments; thus, the aim of the current study is to assess the activated sludge-based effluent treatment system adopted by it. Microscopic analyses of microfauna and biological floc structure, as well as sludge physicochemical and sedimentability analyses, were carried out. The sludge was classified as Pin-Point. Although Arcella sp. prevalence has given sludge a satisfactory clearance feature, the presence of Aspidisca sp. and Trachelophyllum sp. in it has indicated nitrification process and significantly old sludge, respectively. These features combined to low protozoan diversity and lack of micrometazoa have evidenced that sludge quality can be improved. Moreover, sludge overall presented poor settleability. Finally, improvements in the activated sludge system were suggested based on results observed in the current study.A geração de efluentes líquidos em uma planta industrial está associada aos processos produtivos eaos funcionários. Esses efluentes necessitam passar por um processo de depuração que os adequem aníveis aceitáveis para descarte, em corpos hídricos receptores, exigidos pela legislação vigente. Aempresa avaliada neste estudo é fabricante de ferramentas e instrumentos de uso doméstico eindustrial. Com isso, o trabalho teve como objetivo realizar a avaliação do seu sistema de tratamentode efluentes por lodos ativados. Foram realizadas análises microscópicas da microfauna e da estruturado floco biológico, além de análises físico-químicas e de sedimentabilidade do lodo. O lodo foiclassificado como Pin-Point. Apesar da predominância de Arcella sp. conferir ao lodo uma característicade boa depuração, a presença de Aspidisca sp. e Trachelophyllum sp. indicam respectivamente, aocorrência de nitrificação e elevada idade do lodo. Essas características associadas à baixa diversidadede protozoários e a ausência de micrometazoários indicam que a qualidade do lodo pode sermelhorada. Além disso, de forma geral, o lodo apresentou má sedimentabilidade. Por fim, a partir dosresultados, realizou-se a proposição de melhorias

Biomonitoramento da poluição do ar: uma chave dicotômica para identificação de espécies de líquens

Biomonitoring has been seen as complementary analysis to physicochemical methods and as a low-cost alternative, mainly for regions lacking air pollution control programs. Despite being the most widely used bioindicator for this type of pollution, lichens are not easily identified and this methodology is restricted to groups of expert researchers. Accordingly, the aim of the present study was to analyze lichen diversity in urban and industrial areas, in order to elaborate a dichotomous key to identify the listed species, based on easily visualized features. Lichens with leaf stalks belonging to family Parmeliaceae and genus Parmotrema were the most abundant, which are known for their resistance to air pollution. The study sites generally presented low lichen diversity, which may also have been influenced by the degree of vegetation around them. This result reinforces the importance of green areas for mitigating air pollution in urban environment. The dichotomous key elaborated for the lichen species found aims to support research, environmental education and management activities, and may expand the use of lichens as air-quality bioindicators.O biomonitoramento tem sido considerado como uma análise complementar aos métodos físicoquímicos e como uma alternativa de baixo custo, principalmente para regiões carentes de programasde controle da poluição do ar. Apesar de ser o bioindicador mais utilizado para esse tipo de poluição,os líquens não são facilmente identificados, ficando essa metodologia restrita a grupos depesquisadores especializados. Nesse sentido, o objetivo do presente estudo foi analisar a diversidadede líquens em áreas urbanas e industriais, a fim de elaborar uma chave dicotômica para identificar asespécies listadas, com características de fácil visualização. Líquens foliosos pertencentes à famíliaParmeliaceae e ao gênero Parmotrema foram os mais abundantes, os quais são conhecidos por suaresistência à poluição atmosférica. Os locais do estudo apresentaram, em geral, baixa diversidade delíquens, a qual pode ter sido influenciada também pela grau de vegetação no entorno dos pontos. Esseresultado reforça a importância de áreas verdes para mitigar a poluição do ar em ambiente urbano. Achave dicotômica elaborada para as espécies de líquens encontradas visa apoiar a pesquisa, atividadesde educação ambiental e de manejo, podendo ampliar o uso de líquens como bioindicadores daqualidade do ar

Impact of urbanization on the water quality of the Uberaba River and tributaries

This paper evaluated the quality of the water in Uberaba River and tributaries. Seven sites were sampled, in a 12-km under the influence of the urban area. The sampling site started upstream the raw-water catchment station, passing through the urban perimeter, upstream and downstream the discharge of the effluent treated by the Sewage Treatment Plant. Benthic macroinvertebrates were collected using a Surber net and, after identification, the indices of BMWP, diversity, equitability and dominance were calculated, besides functional group analysis. In each sampling site, it was analyzed microbiological and physicochemical parameters in order to identify possible domestic and/or industrial pollution sources. A rapid assessment protocol (RAP) was also applied, and land use and occupation aspects were mapped. The water collected in the furthest sampling site from the urban area and with vegetation in the surroundings, presented satisfactory quality, based in BMWP index. However, this quality dropped to very poor as the river water crossed the urban perimeter. The land use and occupation map showed a predominance of agriculture/pasture and urbanization. In addition, the presence of E. coli and the high levels recorded for some metals (principally cooper and cadmium), suggested contamination of the water with domestic and industrial effluents.

O uso da suplementação materna para prevenção de defeitos congênitos e outros agravos na gestação / The use of maternal supplementation to prevent congenital defects and other aggregates in pregnancy

Objetivo: Analisar quais os artigos disponíveis na literatura que apresentam informações consistentes sobre o papel da suplementação materna na prevenção de malformações congênitas e agravos na gestação. Método: A Revisão Integrativa de Literatura (RIL) foi o método escolhido, com o objetivo de reunir uma coleção de saberes científicos e estatísticos acerca do tema, tornando-os acessíveis a todos os interessados. Neste estudo, utilizou-se para isso a questão norteadora: “Quais estudos presentes na literatura abordaram suplementações materna como terapia preventiva de doenças ou malformações congênitas? ” Para tanto, foi aplicada uma metodologia eficiente na seleção e abordagem dos artigos, por meio de critérios de inclusão e exclusão bem definidos. Resultados e discussão: Após a aplicação dos filtros foram encontrados 12 artigos, e destes, 10 foram selecionados por corresponderem aos critérios de inclusão. Houve, a partir dessa seleção inicial, a análise minuciosa dos artigos, por meio de um quadro sinóptico, contendo o código dado a cada artigo, o nome, o ano, objetivo, método, resultados e conclusão, além da classificação de seu nível de evidência. Feito isso, foram criadas as categorias com os tópicos que mais prevaleceram nesses trabalhos. Sendo as três categorias: a incerteza entre a dose benéfica dos suplementos recomendados para as gestantes, o uso da suplementação durante a gestação para prevenção de anormalidades no tubo neural e comparação entre a utilização de multivitamínicos com a utilização de apenas ácido fólico. Conclusão: A suplementação materna é fundamental na prevenção de anormalidades congênitas e também de determinadas doenças maternas, principalmente quando administrados nos períodos pré-gestacional e durante a gestação. Destacamos a importância de analisar cada mulher individualmente para a prescrição da suplementação, pois, dessa forma, é possível aumentar a adesão à suplementação no período adequado.

Islet neogenesis-associated protein signaling in neonatal pancreatic rat islets: Involvement of the cholinergic pathway

Islet neogenesis associated protein (INGAP) increases islet mass and insulin secretion in neonatal and adult rat islets. In the present study, we measured the short- and long-term effects of INGAP-PP (a pentadecapeptide having the 104-118 amino acid sequence of INGAP) upon islet protein expression and phosphorylation of components of the P13K, MAPK and cholinergic pathways, and on insulin secretion. Short-term exposure of neonatal islets to INGAP-PP (90 s, 5, 15, and 30 min) significantly increased Akt1-Ser473 and MAPK3/1-Thr202/ Tyr204 phosphorylation and INGAP-PP also acutely increased insulin secretion from islets perifused with 2 and 20 mM glucose. Islets cultured for 4 days in the presence of INGAP-PP showed an increased expression of Akt1, Frap1, and Mapk1 mRNAs as well as of the muscarinic M3 receptor subtype, and phospholipase C (PLC)-β2 proteins. These islets also showed increased Akt1 and MAPK3/1 protein phosphorylation. Brief exposure of INGAP-PP-treated islets to carbachol (Cch) significantly increased P70S6K-Thr389 and MAPK3/1 phosphorylation and these islets released more insulin when challenged with Cch that was prevented by the M3 receptor antagonist 4-DAMP, in a concentration-dependent manner. In conclusion, these data indicate that short- and long-term exposure to INGAP-PP significantly affects the expression and the phosphorylation of proteins involved in islet P13K and MAPK signaling pathways. The observations of INGAPP-PP-stimulated up-regulation of cholinergic M3 receptors and PLC- proteins, enhanced P70S6K and MAPK3/1 phosphorylation and Cch-induced insulin secretion suggest a participation of the cholinergic pathway in INGAP-PP-mediated effects.Facultad de Ciencias MédicasCentro de Endocrinología Experimental y Aplicad

Delineation of management zones using mobile measurements of soil apparent electrical conductivity and multivariate geostatistical techniques

Site-specific management promotes the identification and management of areas within the field, which represent subfield regions with homogeneous characteristics (management zones). However, determination of subfield areas is difficult because of the complex combination of factors which could affect crop yield. One possibility to capture yield variability is the use of soil physical properties to define the management zones as they are related to plant available water. With the aim of characterizing the spatial variability of the main soil physical variables and using this information to determine potential management zones, soil samples were taken from 70 locations in a 33-ha field in Badajoz, southwestern Spain. Firstly, accurate spatial distribution maps of the soil attributes were generated by using regression kriging as the most suitable algorithm in which exhaustive secondary information on soil apparent electrical conductivity (ECa) was incorporated. ECa measurements were carried out with a Veris 3100 operating in both shallow (0–30 cm), ECs, and deep (0–90 cm), ECd,mode. Clay, coarse sand and fine sand were the soil physical properties which exhibited higher correlation with ECa (positively correlated with the finer texture component, clay, and negatively correlated with the coarser ones, coarse and fine sands), particularly with ECs. Thus, this was the secondary variable used to obtain the kriged maps. Later, principal component analysis and fuzzy cluster classification were performed to delineate management zones, resulting in two subfields to be managed separately. This number of subfields was determined using the fuzzy performance index and normalized classification entropy as the way to optimize the classification algorithm