Europäisches Journal für Experimentalbiologie Offener Zugang

Abstrakt

Action of simvastatin on the attenuation of inflammation in 3T3 -L1 adipocytes is related to PPARs modulation

Mariana Kuniyoshi, Renata Nakamichi, Silmara de Melo Carmona, Maria Aparecida da Glória, Maria Aparecida Dalboni, Beata Marie Redublo Quinto, Marcelo Costa Batista

Visceral obesity is the main foundation to the development of Metabolic Syndrome (MS), representing the pathophysiological basis related to the epidemic burden of cardiovascular disease. The increase in secretion of biologically active molecules such as leptin, a pro-inflammatory adipokine, results in a significant impact on the progression of the MS. Based on its pleiotropic and anti-atherogenic actions, the use of statins targeting inflammation has been advocate as a strategy for reducing atherosclerotic vascular disease. The aim of this study was to investigate the in vitro effect of simvastatin on leptin secretion and expression in mature 3T3-L1 adipocytes after stimulation with TNF-α. In addition, we analyzed the potential effects of simvastatin on the modulation 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 pro-inflammatory proteins, specifically leptin in adipocitary cell models. Treatment with simvastatin reversed the impact of the inflammatory process induced by TNF-α administration in adipocytes. We have also demonstrated that there was a reduced expression of PPAR-α and PPAR-γ receptors when submitted to the inflammatory stimulus. The treatment of those cells with simvastatin reversed the attenuation in the expression of these receptors in cells exposed to TNF-α.

We reiterate, at the cellular level, the integral inflammatory state of obesity-related MS and the association between increased syntheses of leptin in this condition. We suggested the beneficial effect of simvastatin in the attenuation of inflammatory response associated with increased TNF-α and a possible relationship of PPARs in the modulation of this response.