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

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 neuro...

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Main Authors: 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
Format: Article
Language:English
Published: BMC 2022-04-01
Series:Chinese Medicine
Subjects:
Online Access:https://doi.org/10.1186/s13020-022-00603-w
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author 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
author_facet 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
author_sort Hongru Gao
collection DOAJ
description 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.
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spelling doaj.art-80a4549cb8e94626a82aa8de53b53abb2022-12-22T01:07:08ZengBMCChinese Medicine1749-85462022-04-0117111510.1186/s13020-022-00603-wThree-dimensional visualization of electroacupuncture-induced activation of brown adipose tissue via sympathetic innervation in PCOS ratsHongru Gao0Xiaoyu Tong1Wei Hu2Yicong Wang3Kuinyu Lee4Xiaoqing Xu5Jiemei Shi6Zhenle Pei7Wenhan Lu8Yuning Chen9Ruonan Zhang10Zheyi Wang11Ziyu Wang12Chengzhi Han13Yu Wang14Yi Feng15State 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 UniversityState 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 UniversityState 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 UniversityState 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 UniversityState 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 UniversityState 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 UniversityState 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 UniversityState 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 UniversityState 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 UniversityState 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 UniversityState 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 UniversityState 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 UniversityState 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 UniversityState 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 UniversityState 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 UniversityState 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 UniversityAbstract 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.https://doi.org/10.1186/s13020-022-00603-wPolycystic ovary syndromeElectroacupunctureBrown adipose tissueSympathetic innervationUncoupling protein 1
spellingShingle 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
Three-dimensional visualization of electroacupuncture-induced activation of brown adipose tissue via sympathetic innervation in PCOS rats
Chinese Medicine
Polycystic ovary syndrome
Electroacupuncture
Brown adipose tissue
Sympathetic innervation
Uncoupling protein 1
title Three-dimensional visualization of electroacupuncture-induced activation of brown adipose tissue via sympathetic innervation in PCOS rats
title_full Three-dimensional visualization of electroacupuncture-induced activation of brown adipose tissue via sympathetic innervation in PCOS rats
title_fullStr Three-dimensional visualization of electroacupuncture-induced activation of brown adipose tissue via sympathetic innervation in PCOS rats
title_full_unstemmed Three-dimensional visualization of electroacupuncture-induced activation of brown adipose tissue via sympathetic innervation in PCOS rats
title_short Three-dimensional visualization of electroacupuncture-induced activation of brown adipose tissue via sympathetic innervation in PCOS rats
title_sort three dimensional visualization of electroacupuncture induced activation of brown adipose tissue via sympathetic innervation in pcos rats
topic Polycystic ovary syndrome
Electroacupuncture
Brown adipose tissue
Sympathetic innervation
Uncoupling protein 1
url https://doi.org/10.1186/s13020-022-00603-w
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