Avaliação dos Efeitos da Administração Crônica de Leptina sobre a Migração e Ativação de Células do Sistema Imune

Leptin is an adipokine secreted mostly by adipose tissue as a product of the ob gene and involved in the regulation of energy expenditure and satiety. Leptin plays an important role in the activation of different cell types. Its signaling occurs from its binding to Ob-R receptors, and its association with the long chain isoform of the receptor (Ob-Rb) is suggested as the main responsible for its anorexigenic effects on the central nervous system and its participation in the regulation of immune responses peripheral regions. As the mass of adipose tissue is increased in obesity, there is a greater production of leptin by mature adipocytes and this leads to elevated levels of circulating leptin. However, under conditions of obesity the development of a central resistance to leptin is observed. The impact of hyperleptinemia on the activation of immune responses is still an unexplored subject and it is not known whether peripheral resistance occurs. The present work aimed to understand the effects of hyperleptinemia induced by chronic leptin administration on the migration and activation of leukocytes in mice of the C57BL/6 lineage in the absence of obesity. We observed that, despite the occurrence of recurrent leptin administrations, chronically stimulated animals continue to respond to some actions triggered by adipokine, presenting subtle weight reduction at each new administration We observed that the chronic stimulus with leptin at 2 mg/kg is able to generate a significant reduction of the glycemia of the animals, which was not observed with the administration of leptin at 1 mg/kg. The evaluation of its effects on the immune system revealed that the chronic stimulus promoted an increase in the migration of mononuclear cells and eosinophils to the peritoneal cavity independently of the leptin concentration administered. It was also verified a greater activation of mononuclear cells in animals stimulated with leptin, evidenced by the increase of CLs in this cellular population. However, there was no change in the secretion of inflammatory mediators such as TNF-\03B1 and IL-1\03B2. It was also found that recurrent leptin stimulation using 1 mg/kg promoted increased eotaxin levels in both the blood and peritoneal cavity, which did not occur when twice the dose was given. This suggests that the release of chemoattractant factors to eosinophils can be modulated by leptin in a dose-dependent manner. Our data suggest the participation of leptin on the migration and activation of immune cells in the peritoneal cavity even when recurrent administrations are performed. Thus, this work contributes to a better understanding of peripheral leptin actions on the leukocyte population in the absence of obesity