Efeitos do destreinamento e da dieta hiperlipidica nos mecanismo moleculares de indução de obesidade e resitencia a insulina / Effects of detraining and high-fat diet on molecular mechanisms of obesity and insulin resistance

AUTOR(ES)
DATA DE PUBLICAÇÃO

2007

RESUMO

The cessation of physical training (detraining) results in rapid fat mass accretion, gain weight and insulin resistance in both humans and animals. However, little is know about the cellular basis for the effect. The aim of this study was to investigate the PI3-kinase/Akt and CAP/Cbl signaling pathways both involved with insulin-stimulated glucose uptake in peripherals tissues (muscle, adipose and liver) in detrained and sedentary animals submitted a high-fat diet. Moreover, we investigated the potential role of the inflammatory pathway in high fat diet-induced insulin resistant in rats detrained. Many mechanisms may contribute to the dysregulation of the insulin-signaling pathway. Several serine/threonine kinases are activated by inflammatory or stressful stimuli and contribute to inhibition of insulin signaling, including JNK, inhibitor of NF-kB kinase (IKK) and others. For these reason, we decided investigate the role of inflammatory process in obesity detraining-induced in development of the insulin-resistance in our experimental model. Finally, is possible that accumulation of intracellular fatty acyl-CoA or other fatty acid metabolites in muscle, either through increased delivery (due to increased caloric intake or alterations in adipocytes fatty acid metabolism) and/or decreased mitochondrial fatty acid oxidation, might be expected to induce insulin resistance in muscle. The UCP-3, present in skeletal muscles, may play a central role in the control of basal metabolic rate and body weight gain. However, there is no data about the effect of detraining on mitochondrial uncoupling in skeletal muscle tissue. We hypothesized that all of these possibilities could to occur under cessation physical exercise (detraining). So, Wistar rats were submitted to swimming training during 8 weeks. Next this period the animals stop the training and received a ichfat diet. The proteins from the insulin signaling and inflammatory pathway were analyzed by immunoprecipitation and immunoblotting. The results demonstrated that detraining result in an increased body mass and rapid body fat accretion. This fact was associated with increases insulin responsiveness through CAP/Cbl pathway in adipose tissue in the detrained animals feeding with a rich-fat diet (HFD) than sedentary rats feeding with HFD. Moreover, in this study, we observed that high-fat diet lead an increased JNK activity, disappearance of IkB and IRS-1 phosphorylation at serine in muscle tissue of the detrained rats when compared to sedentary animals. These results indicate that this serine kinases is one of the causes of insulin resistance to found in the insulin tolerance test. Finally, the increased intramyocellular lipid content and a lesser UCP-3 expression in muscle of detrained rats that receive a high-fat diet interfere with insulin signaling and with body weight gain. In conclusion, the detraining is characterized to several molecular alterations that contribute to more body weight gain, fat accretion and insulin resistance when associated with a fed rich-fat diet

ASSUNTO(S)

inflammation inflamação distraining obesity destreinamento fisico obesidade insulin resistance resistencia a insulina

ACESSO AO ARTIGO

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