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

Hongru Gao; Xiaoyu Tong; Wei Hu; Yicong Wang; Kuinyu Lee; Xiaoqing Xu; Jiemei Shi; Zhenle Pei; Wenhan Lu; Yuning Chen; Ruonan Zhang; Zheyi Wang; Ziyu Wang; Chengzhi Han; Yu Wang; Yi Feng

doi:10.1186/s13020-022-00603-w

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

Chin Med. 2022 Apr 18;17(1):48. doi: 10.1186/s13020-022-00603-w.

Authors

Hongru Gao^#¹, Xiaoyu Tong^#¹, Wei Hu^#¹, Yicong Wang¹, Kuinyu Lee¹, Xiaoqing Xu¹, Jiemei Shi¹, Zhenle Pei¹, Wenhan Lu¹, Yuning Chen¹, Ruonan Zhang¹, Zheyi Wang¹, Ziyu Wang¹, Chengzhi Han¹, Yu Wang¹, Yi Feng²

Affiliations

¹ State Key Laboratory of Medical Neurobiology, Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Institutes of Brain Science, Brain Science Collaborative Innovation Center, Fudan Institutes of Integrative Medicine, Fudan University, Shanghai, 200032, China.
² State Key Laboratory of Medical Neurobiology, Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Institutes of Brain Science, Brain Science Collaborative Innovation Center, Fudan Institutes of Integrative Medicine, Fudan University, Shanghai, 200032, China. fengyi17@fudan.edu.cn.

^# Contributed equally.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: Our study highlights the significant role of BAT and its sympathetic innervations in PCOS and in EA therapy.

Keywords: Brown adipose tissue; Electroacupuncture; Polycystic ovary syndrome; Sympathetic innervation; Uncoupling protein 1.

Abstract

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