Examinando por Autor "Fardella, C.E."
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Ítem Eplerenone Implantation Improved Adipose Dysfunction Averting RAAS Activation and Cell Division(Frontiers Media S.A., 2020-04) Vecchiola, A.; Fuentes, C.A.; Solar, I.; Lagos, C.F.; Opazo, M.C.; Muñoz-Durango, N.; Riedel, C.A.; Owen, G.I.; Kalergis, A.M.; Fardella, C.E.Introduction: Mineralocorticoid receptor (MR) activation within adipose tissue, triggers inflammation and metabolic syndrome development. The pharmacological blockade of MR provides beneficial effects for adipose tissue. Our study evaluates the impact of eplerenone implantation upon obesity. Experimental approach: A group of mice with implanted placebo pellets were fed using two types of diet, a normal (ND) or a high fat (HFD) diet. Additionally, a group of mice fed HFD were implanted with an eplerenone pellet. Metabolic and biochemical parameters were assessed in each animal group. Adipocyte size and lipid accumulation were investigated in the liver and adipose tissue. We evaluated the components of renin-angiotensin-aldosterone system (RAAS) locally in adipose tissue. Key results: Eplerenone reduced HFD-induced body weight gain, fasting glucose levels, fat accumulation, HFD-induced adipocyte size and liver lipid accumulation and improved glucose tolerance. In the adipose tissue, HFD significantly increased the mRNA levels of the RAAS molecules relative to the ND group. Eplerenone lowered RAAS mRNA levels, components of lipid metabolism and markers of inflammation in HFD-fed animals. Conclusion: MR antagonism with eplerenone diminishes insulin resistance that is related to obesity partly via a reduction of RAAS activation, inflammatory progression and cytokines induction. This suggests that eplerenone should be further studied as a therapeutic option for obesity and overweight. © Copyright © 2020 Vecchiola, Fuentes, Solar, Lagos, Opazo, Muñoz-Durango, Riedel, Owen, Kalergis and Fardella.Ítem Modulation of immunity and inflammation by the Mineralocorticoid receptor and Aldosterone(Hindawi Publishing Corporation, 2015) Muñoz-Durango, N.; Vecchiola, A.; Gonzalez-Gomez, L.M.; Simon, F.; Riedel, C.A.; Fardella, C.E.; Kalergis, A.M.The mineralocorticoid receptor (MR) is a ligand dependent transcription factor. MR has been traditionally associated with the control of water and electrolyte homeostasis in order to keep blood pressure through aldosterone activation. However, there is growing evidence indicating that MR expression is not restricted to vascular and renal tissues, as it can be also expressed by cells of the immune system, where it responds to stimulation or antagonism, controlling immune cell function. On the other hand, aldosterone also has been associated with proinflammatory immune effects, such as the release of proinflammatory cytokines, generating oxidative stress and inducing fibrosis. The inflammatory participation of MR and aldosterone in the cardiovascular disease suggests an association with alterations in the immune system. Hypertensive patients show higher levels of proinflammatory mediators that can be modulated by MR antagonism. Although these proinflammatory properties have been observed in other autoimmune and chronic inflammatory diseases, the cellular and molecular mechanisms that mediate these effects remain unknown. Here we review and discuss the scientific work aimed at determining the immunological role of MR and aldosterone in humans, as well as animal models. © 2015 N. Muñoz-Durango et al.