2-甲氧基雌二醇通过调节脂肪组织巨噬细胞浸润和免疫表型抑制高脂肪饮食诱导的大鼠肥胖。
2-Methoxyestradiol inhibits high fat diet-induced obesity in rats through modulation of adipose tissue macrophage infiltration and immunophenotype.
机构信息
Clinical Pharmacy Practice Department, Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, P.O. Box 43, Cairo, 11837, Egypt; The Center for Drug Research and Development (CDRD), Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, P.O. Box 43, Cairo, 11837, Egypt.
Clinical Pharmacy Practice Department, Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, P.O. Box 43, Cairo, 11837, Egypt; The Center for Drug Research and Development (CDRD), Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, P.O. Box 43, Cairo, 11837, Egypt.
出版信息
Eur J Pharmacol. 2020 Jul 5;878:173106. doi: 10.1016/j.ejphar.2020.173106. Epub 2020 Apr 10.
Recently, experimental studies demonstrated that 2-methoxyestradiol (2ME2) ameliorates high fat diet (HFD)-induced obesity and restores insulin sensitivity. However, the mechanisms underlying these effects are unveiled yet. The current study was undertaken to test the hypothesis that 2ME2 exerts its effects by modulating adipose tissue macrophages (ATMs) accumulation, polarization and immunophenotypes. The experiment was carried out in males Wistar rats (n = 28) for 13 consecutive weeks. In HFD-fed group; body weight, glucose intolerance, serum insulin, HOMA-IR, lipid profile and adipose tissue (AT) weight were significantly higher compared to normal standard diet (NSD)- fed rats. However, treatment of HFD-fed rats with 2ME2 (200 μg/kg/day; i.p. from the beginning of the 9th week) resulted in significant enhancements in all these parameters as compared to HFD-fed rats. Treatment with 2ME2 was associated with a significant reduction in macrophage infiltration in the AT, shifting macrophage polarization towards M2 phenotype as indicated by significant decrease in the expression of pro-inflammatory M1 macrophages markers (IL-6, IL-1β, CD11c and iNOS) and concurrent significant increase in the M2 anti-inflammatory macrophage markers (Arginase 1 and IL-10). 2ME2 ameliorates HFD-induced obesity and glucose intolerance through inhibition of ATM infiltration in AT and shifting macrophage polarization from pro-inflammatory M1 to M2 anti-inflammatory phenotypes.
最近的实验研究表明，2-甲氧基雌二醇（2ME2）可改善高脂肪饮食（HFD）诱导的肥胖并恢复胰岛素敏感性。然而，这些作用的机制尚未阐明。本研究旨在验证 2ME2 通过调节脂肪组织巨噬细胞（ATMs）积聚、极化和免疫表型发挥作用的假设。该实验在雄性 Wistar 大鼠（n=28）中连续进行了 13 周。与正常标准饮食（NSD）喂养的大鼠相比，HFD 喂养的大鼠体重、葡萄糖耐量、血清胰岛素、HOMA-IR、血脂谱和脂肪组织（AT）重量显著升高。然而，与 HFD 喂养的大鼠相比，用 2ME2（200μg/kg/天；从第 9 周开始腹腔注射）治疗 HFD 喂养的大鼠可显著改善所有这些参数。用 2ME2 治疗与 AT 中巨噬细胞浸润的显著减少有关，巨噬细胞极化向 M2 表型转变，表明促炎 M1 巨噬细胞标志物（IL-6、IL-1β、CD11c 和 iNOS）的表达显著下降，同时 M2 抗炎巨噬细胞标志物（精氨酸酶 1 和 IL-10）显著增加。2ME2 通过抑制 AT 中 ATM 的浸润和将巨噬细胞极化从促炎 M1 转变为抗炎 M2 表型来改善 HFD 诱导的肥胖和葡萄糖不耐受。
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