Department of Endocrinology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
Millennium Institute on Immunology and Immunotherapy IMII, Santiago, Chile.
Front Endocrinol (Lausanne). 2020 Apr 21;11:223. doi: 10.3389/fendo.2020.00223. eCollection 2020.
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. 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. 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. 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.
醛固酮受体 (MR) 在脂肪组织中的激活会引发炎症和代谢综合征的发展。MR 的药理学阻断为脂肪组织提供了有益的效果。我们的研究评估了依普利酮植入对肥胖的影响。一组接受安慰剂植入的小鼠接受两种饮食，一种是正常饮食（ND）或高脂肪饮食（HFD）。此外，一组接受 HFD 的小鼠被植入了依普利酮植入物。对每组动物的代谢和生化参数进行了评估。在肝脏和脂肪组织中研究了脂肪细胞大小和脂质积累。我们评估了脂肪组织中肾素-血管紧张素-醛固酮系统 (RAAS) 的成分。依普利酮可减少 HFD 引起的体重增加、空腹血糖水平、脂肪堆积、HFD 诱导的脂肪细胞大小和肝脏脂质积累，并改善葡萄糖耐量。在脂肪组织中，HFD 与 ND 组相比，RAAS 分子的 mRNA 水平显著增加。依普利酮降低了 HFD 喂养动物的 RAAS mRNA 水平、脂质代谢成分和炎症标志物。MR 拮抗剂依普利酮通过减少 RAAS 激活、炎症进展和细胞因子诱导，减轻与肥胖相关的胰岛素抵抗。这表明依普利酮应作为肥胖和超重的治疗选择进一步研究。
