The food intake and energy expenditure are regulated by specific neurons located in the hypothalamus. During the last two decades, the location of leptin receptors in hypothalamic nuclei and the description of the intracellular signaling triggered by this hormone in hypothalamic neurons were crucial to understanding the control of food intake and energy expenditure. The eating disorders are associated such as obesity; are related to leptin signaling dysfunctions in the hypothalamus. The subclinical inflammatory process observed in experimental models of obesity is associated with several mechanisms of leptin resistance in the hypothalamus and result in increased food intake and body weight gain. On the other hand, it has been demonstrated that exercise, by increasing the expression of Interleukin-6 (IL-6), is able to increase the leptin sensitivity in the hypothalamus of obese animals, however, these mechanisms remain partially known. Recently, the protein S1PR1 (sphingosine-1-phosphate receptor-1) was described as a molecule with high capacity to exert potent synergistic effects on the leptin signaling, supporting the activation of the Jak2/STAT3 after IL-6 stimulus in different cell lines. Thus, the aims of the project are investigate the effects of exercise and IL-6 on the leptin sensitivity and on S1PR1 activity of in the hypothalamus of obese rodents. We believe that this project will contribute to characterize the participation of S1PR1 in leptin signaling in the hypothalamus and to determine the effects of exercise on the neuronal S1PR1 activity.
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