Three-dimensional visualization of electroacupuncture-induced activation of brown adipose tissue via sympathetic innervation in PCOS rats.

Three-dimensional visualization of electroacupuncture-induced activation of brown adipose tissue via sympathetic innervation in PCOS rats.
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电针仪诱导的三维可视化通过PCOS大鼠的交感神经神经神经化激活了棕色脂肪组织。

DOI:
10.1186/s13020-022-00603-w
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发表时间:
2022-04-18
期刊:
影响因子:
4.9
通讯作者:
Feng, Yi
Feng, Yi
中科院分区:
医学3区
文献类型:
--
作者:
Gao, Hongru;Tong, Xiaoyu;Hu, Wei;Wang, Yicong;Lee, Kuinyu;Xu, Xiaoqing;Shi, Jiemei;Pei, Zhenle;Lu, Wenhan;Chen, Yuning;Zhang, Ruonan;Wang, Zheyi;Wang, Ziyu;Han, Chengzhi;Wang, Yu;Feng, Yi

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低频电针可以改善多囊卵巢综合征(PCOS)患者的肥胖和生殖功能障碍,对PCOS样大鼠的进一步研究表明,电针可以影响白色脂肪组织。然而,棕色脂肪组织(BAT)在PCOS和EA治疗后的功能和神经调节仍然未知。本研究旨在探讨BAT在PCOS样大鼠中的作用及其与电针的关系,并探讨BAT与激活分子相关的三维神经支配。雌性大鼠(21日龄)分别皮下植入双氢睾酮或喂饲高脂饲料建立PCOS样和肥胖模型,然后电针“归来”和“三阴交”穴4周。本研究采用形态学、三维成像、分子生物学等实验技术对交感神经及其活动进行了研究。PCOS样大鼠表现出明显的体重增加和生殖功能障碍,除了没有生殖功能障碍外,与肥胖大鼠相似。体重增加主要由白色脂肪组织增加引起,BAT异常减少。由于电针双侧“归来”、“三阴交”穴可改善大鼠的脂代谢和生殖功能障碍,尤其是改善BAT的恢复,因此我们进一步研究了BAT的神经调节和炎症反应,并确定了交感神经标志物酪氨酸羟化酶是交感神经的关键因子之一。改良的脂肪清除技术和3D高分辨率成像显示,弯曲或分散的交感神经,而不是扭曲的血管,被重建,并与BAT的激活,可能是EA治疗的功能目标。我们的研究强调了BAT及其交感神经支配在PCOS和EA治疗中的重要作用。在线版本包含补充材料,可通过10.1186/s13020-022-00603-w获得。
Low-frequency electroacupuncture (EA) has been shown to ameliorate obesity and reproductive dysfunctions in patients with polycystic ovary syndrome (PCOS), and further explorations in PCOS-like rats showed that EA could affect white adipose tissue. However, the function and neuromodulation of brown adipose tissue (BAT) in PCOS and after EA treatment have remained unknown. The present study focused on the role of BAT in PCOS-like rats and its relationship with EA and characterized the three-dimensional (3D) innervation of BAT associated with activation molecules. Female rats (21 days old) were implanted with dihydrotestosterone or fed with a high fat diet to establish PCOS-like and obesity models, respectively, and then EA treatment at “Guilai” (ST 29) and “Sanyinjiao” (SP 6) was carried out for 4 weeks. In the present study, morphological analysis, 3D imaging, molecular biology, and other experimental techniques were used to study the sympathetic nerves and activity of BAT. PCOS-like rats showed both obvious weight gain and reproductive dysfunction, similar to what was seen in obese rats except for the absence of reproductive dysfunction. The body weight gain was mainly caused by an increase in white adipose tissue, and there was an abnormal decrease in BAT. Because both the lipid metabolism and reproductive disorders could be improved with bilateral EA at “Guilai” (ST 29) and “Sanyinjiao” (SP 6), especially the restoration of BAT, we further investigated the neuromodulation and inflammation in BAT and identified the sympathetic marker tyrosine hydroxylase as one of the key factors of sympathetic nerves. Modified adipo-clearing technology and 3D high-resolution imaging showed that crooked or dispersed sympathetic nerves, but not the twisted vasculature, were reconstructed and associated with the activation of BAT and are likely to be the functional target for EA treatment. Our study highlights the significant role of BAT and its sympathetic innervations in PCOS and in EA therapy. The online version contains supplementary material available at 10.1186/s13020-022-00603-w.
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