RESUMO
Sulforaphane (SFN) is a dietary component with multiple bioactivities; however, its role in obesity-related metabolic derangement remains unclear. Here, the effect of SFN on the glucose intolerance of obese mice and the underlying mechanism were determined. C57B/6J male mice were randomly divided into two groups, having free access to water and a normal-fat diet (ND, n = 6) or a high-fat diet (HFD, n = 33) for 8 weeks; thereafter twelve mice having the greatest weight gain among the HFD-fed mice were considered as obese mice. These obese mice were randomly divided into two groups and treated orally for 6 weeks with or without SFN (100 µmol per kg bw, 3 times per week). During this period the animals were continuously maintained on a ND or a HFD. Blood glucose and serum insulin were examined; then glucose tolerance and insulin resistance were evaluated. In addition, the expression of insulin signaling pathway-related genes in the muscle was determined. Our data showed that the obese mice presented a marked insulin resistance and glucose intolerance as compared to the control group, while SFN treatment exerted a prominently protective effect. In addition, the SFN-treated obese mice had a significantly increased insulin receptor substrate 1 (IRS-1) protein level (P < 0.05), markedly elevated Akt activation, as well as dramatically enhanced phosphorylation of PDK-1 (P < 0.05) when compared with the SFN-untreated obese mice. Moreover, the SFN-treated obese mice exhibited a significantly enhanced translocation of GLUT4 (P < 0.05) to the plasma membrane in the muscle compared to the obese mice without SFN treatment. In conclusion, our results support the notion that SFN acts as a promising agent to improve glucose tolerance through the up-regulation of insulin signaling mainly involving the IRS-1/Akt/GLUT4 pathway in the muscle.
Assuntos
Intolerância à Glucose/tratamento farmacológico , Insulina/metabolismo , Isotiocianatos/administração & dosagem , Animais , Glicemia/metabolismo , Dieta Hiperlipídica/efeitos adversos , Intolerância à Glucose/genética , Intolerância à Glucose/metabolismo , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Humanos , Insulina/genética , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Piruvato Desidrogenase Quinase de Transferência de Acetil , Transdução de Sinais/efeitos dos fármacos , Sulfóxidos , Regulação para Cima/efeitos dos fármacosRESUMO
Human enterovirus 71(EV71), one of the major pathogens of the hand, foot and mouth disease (HFMD), causes skin rashes in palms, feet and mouth ulcers and complication in the central nervous system such as aseptic meningitis and acute flaccid paralysis that may lead to death. EV71 infection has been reported to be associated with many outbreaks of HFMD worldwide, especially the great outbreaks that occurred in the Asia-Pacific region and caused numerous death since 1997. The studies of molecular epidemiology and evolution of EV71 are important for the prevention and control of HFMD since no vaccines and antiviral drugs have been developed except symptomatic treatment for HFMD. In this review, we summarize genotype classification, temporal and spatial distribution, evolutionary characteristics and modes of EV71 as well as typical EV71 epidemics. Further studies on EV71 and HFMD may lead to better understanding of pathological mechanisms of EV71, development of antiviral drugs and prevention and control of HFMD.
