Physical Exercise Reduces Circulating Lipopolysaccharide and TLR4 Activation and Improves Insulin Signaling in Tissues of DIO Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)OBJECTIVE-Insulin resistance in diet-induced obesity (DIO) is associated with a chronic systemic low-grade inflammation, and Toll-like receptor 4 (TLR4) plays an important role in the link among insulin resistance, inflammation, and obesity. The current study aimed to analyze the effect of exercise on TLR4 expression and activation in obese rats and its consequences on insulin sensitivity and signaling. RESEARCH DESIGN AND METHODS-The effect of chronic and acute exercise was investigated on insulin sensitivity, insulin signaling, TLR4 activation, c-Jun NH(2)-terminal kinase (JNK) and I kappa B kinase (IKK beta) activity, and lipopolysaccharide (LPS) serum levels in tissues of DIO rats. RESULTS-The results showed that chronic exercise reduced TLR4 mRNA and protein expression in liver, muscle, and adipose tissue. However, both acute and chronic exercise blunted TLR4 signaling in these tissues, including a reduction in JNK and IKK beta phosphorylation and IRS-1 serine 307 phosphorylation, and, in parallel, improved insulin-induced IR, IRS-1 tyrosine phosphorylation, and Akt serine phosphorylation, and reduced LPS serum levels. CONCLUSIONS-Our results show that physical exercise in DIO rats, both acute and chronic, induces an important suppression in the TLR4 signaling pathway in the liver, muscle, and adipose tissue, reduces LPS serum levels, and improves insulin signaling and sensitivity. These data provide considerable progress in our understanding of the molecular events that link physical exercise to an improvement in inflammation and insulin resistance. Diabetes 60:784-796, 2011603784796Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de PesquisaINCT-Obesidade e DiabetesFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Generalised Rational Bias in Financial Forecasts

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Experimentally induced intravaginal Tritrichomonas foetus infection in a mouse model Infecção experimental intravaginal com Tritricho-monas foetus em modelo camundongo

The interest to develop research on the host-parasite relationship in bovine tritrichomonosis has accomplished the use of experimental models alternative to cattle. The BALB/c mouse became the most appropriate species susceptible to vaginal Tritrichomonas foetus infection requiring previous estrogenization. For the need of an experimental model without persistent estrogenization and with normal estrous cycles, the establishment and persistence of vaginal infection on BALB/c mouse with different concentrations of T. foetus in two experimental groups was evaluated. Group A was treated with 5mg of b-estradiol 3-benzoate to synchronize the estrous, 48 hours before the T. foetus vaginal inoculation, and Group B was inoculated in natural estrus. At 5-7 days after treatment, estrogenic effect decreased allowing all animals to cycle regularly during the experiment. From the first week post-infection, samples of vaginal mucus were taken from all animals during 34 weeks, in order to evaluate the course of infection and the stage of the estrus cycle. Group A showed 93.6% of infected animals, and Group B showed 38%. Different doses of T. foetus were assayed to establish the vaginal infection, with a persistence of 34 weeks. Although different behavior was observed in each subgroup belonging to either Group A or Group B, there were no significant differences among the infecting doses used. The b-estradiol 3-benzoate treatment had a favorable effect on the establishment of the infection (P<0.0001), but it did not influence its persistence (P=0.1097). According to the results, an experimental mouse model is presented, appropriate for further studies on mechanisms of pathogenicity, immune response, protective evaluation of immunogen and therapeutic effect of drugs.<br>A necessidade de esclarecer a relação agente-hospedeiro na tricomoníase bovina deu motivo para o uso de modelos experimentais alternativos ao bovino. O camundongo BALB/c resultou como espécie mais adequada para a infeção vaginal com Tritrichomonas foetus, requerendo uma estrogenização prévia. Visando a necessidade de um modelo experimental sem estrogenização persistente e com ciclos estrais normais, foi avaliada a instalação e persistência da infeção vaginal no camundongo BALB/c com diferentes quantidades de T. foetus, em dois grupos experimentais. O Grupo A foi tratado com 5µg de 3-benzoato de beta estradiol, para sincronizar o estro, 48 h antes da inoculação vaginal com T. foetus, e o Grupo B foi inoculado durante o estro natural. O efeito do 3-benzoato de beta estradiol decresceu gradualmente. A totalidade dos animais ciclaram regularmente após 5-7 dias pós-tratamento. Após a primeira semana pós-infecção, todos os animais foram amostrados durante 34 semanas, para avaliar o andamento da infeção vaginal e o estádio de cío. O Grupo A apresentou 93,6% de animais infetados e o Grupo B 38%. Com diferentes dosagens de T. foetus se obteve a instalação e persistência da infecção vaginal durante 34 semanas. Embora tenham-se registrados diferentes comportamentos entre cada um dos lotes dos Grupos A e B, não houveram diferenças significativas entre as doses infectantes. O tratamento com 3-benzoato de beta estradiol teve efeito favorável na instalação da infecção (P<0,0001), porém não teve influência na persistência (P= 0,1097). Em função dos resultados obtidos, apresenta-se um modelo experimental em camundongo, adequado para aprofundar estudos sobre mecanismos de patogenicidade, resposta imune, avaliação protetora de imunógenos e o efeito terapêutico de fármacos