Hyperhomocysteinemia Promotes Insulin Resistance and Adipose Tissue Inflammation in PCOS Mice Through Modulating M2 Macrophage Polarization via Estrogen Suppression
Hyperhomocysteinemia Promotes Insulin Resistance and Adipose Tissue Inflammation in PCOS Mice Through Modulating M2 Macrophage Polarization via Estrogen Suppression
复制标题
高同型半胱氨酸血症通过雌激素抑制调节 M2 巨噬细胞极化，促进 PCOS 小鼠的胰岛素抵抗和脂肪组织炎症。
DOI：
10.1210/en.2017-00039
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发表时间：
2017-05-01
期刊：
影响因子：
4.8
通讯作者：
Qiao, Jie
中科院分区：
文献类型：
--
作者：
Qi, Xinyu;Zhang, Bochun;Qiao, Jie
多囊卵巢综合征(PCOS)患者血清同型半胱氨酸(Hcy)水平明显升高。然而，高同型半胱氨酸血症(HHcy)在多囊卵巢综合征(PCOS)发生发展中的具体作用尚未见报道。脂肪组织炎症的特点是巨噬细胞的浸润，巨噬细胞在糖耐量和胰岛素抵抗的发病机制中起关键作用。本研究用脱氢表雄酮(DHEA)和/或高蛋氨酸饮食治疗C57BL/6小鼠，建立PCOS和HHcy小鼠模型。我们发现，DHEA诱导了PCOS样表型、发情周期不规则、体重增加、性激素分泌异常、葡萄糖和胰岛素抵抗以及多囊卵巢。HHcy进一步加强了DHEA对PCOS样鼠的代谢、内分泌、激素和形态变化的影响。此外，HHcy还可减轻DHEA引起的小鼠血清雌激素水平的升高。此外，HHcy可能会加重PCOS样鼠的胰岛素抵抗，很可能是通过抑制雌激素来调节巨噬细胞M1/M2极化途径。最重要的是，我们的临床数据显示，多囊卵巢综合征患者的血清Hcy水平升高。这些发现加深了我们对HHcy在PCOS发生发展中的病理作用的认识，为PCOS的临床治疗提供了一个有希望的靶点。
It has been shown that serum homocysteine (Hcy) levels are higher in women with polycystic ovary syndrome (PCOS). However, the specific role of hyperhomocysteinemia (HHcy) in the development of PCOS has never been reported. Adipose tissue inflammation is featured by the infiltration of macrophages, which plays a critical role in the pathogenesis of glucose and insulin intolerance. In this study, C57BL/6 mice were treated with dehydroepiandrosterone (DHEA) and/or a high methionine diet to induce PCOS and HHcy mice models. We showed that DHEA induced a PCOS-like phenotypes, irregular estrous cycles, weight gain, abnormal sex hormone production, glucose and insulin resistance, and polycystic ovaries. HHcy further intensified the effects DHEA on the metabolic, endocrinal, hormonal, and morphological changes in PCOS-like mice. In addition, HHcy attenuated the DHEA-induced increase in serum estrogen levels in mice. Furthermore, HHcy may exacerbate the insulin resistance in PCOS-like mice, most likely through modulating the macrophage M1/M2 polarization pathways via the suppression of estrogen. Most important, our clinical data showed that therewere increases in serum Hcy levels in patients with PCOS. These findings deepen our understanding of the pathological roles of HHcy in the development of PCOS and provide a promising target for PCOS therapy in clinical application.