Estudo do efeito da sinvastatina na expressão gênica dos PPARs α e γ e na expressão e secreção de leptina em adipócitos 3T3-L1 submetidos a estímulo inflamatório

• Ano de defesa: 2016
• Autor(a) principal: Kuniyoshi, Mariana [UNIFESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Hypertension; Simvastatin; Pressoreceptors; Denervation; Hipertensão; Sinvastatina; Pressorreceptores; Denervação
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=4823677; http://repositorio.unifesp.br/handle/11600/47025

Visceral obesity is considered important in the development of Metabolic Syndrome (MS), and as pathophysiological basis related to epidemic incidence of cardiovascular events. The excessive expansion of adipose tissue mass resulting in hypertrophic adipocytes can be attributed as a significant cause for inflammation development. The increase in secretion of biologically active molecules such as leptin, a pro-inflammatory adipokines, results in a significant impact on the progression of the MS. The administration of drugs, used primarily for the treatment of dyslipidemia in pleiotropic actions and antiatherogenic has been a major focus of recent studies approaching inflammation as a strategy for reducing cardiovascular risk. Thus, the objective of this study was to investigate the effect of simvastatin on the leptin secretion and expression in mature adipocytes derived from 3T3-L1 cell line, at baseline and after stimulation with TNF- α, mimicking the inflammatory state of the MS. In addition, we analyzed the potential effects of simvastatin on reversal of the inflammatory response in 3T3-L1 adipocytes and possible involvement of receptors activated by peroxisome proliferators-alpha (PPAR-α) and gamma (PPAR-γ) in such conditions. Our results consolidate the concept of MS as an inflammatory disease caused by increased production of mediators of proinflammatory proteins, specifically leptin, in adipocitary cell models. We have also demonstrated that there was reduced expression of PPAR-α and PPAR-γ receptors, when subject to inflammatory stimulus. By contrast, we observed an increase in expression of these receptors in cells pre-treated with simvastatin and exposed to TNF-α stimulus. From the analysis of our results, we support, at the cellular level, the integral inflammatory state of obesity¬related to MS. We also demonstrated the beneficial effect of simvastatin in attenuating the inflammatory response associated with increased TNF-α and a possible relationship of the PPARs in the modulation of this response.