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 (WAT). 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 it characterized the three-dimensional (3D) innervation of BAT associated with activation molecules.
Methods: Twenty-one-day-old female rats were implanted with dihydrotestosterone or fed high fat diet respectively to establish PCOS-like and obesity models, and then EA treatment at “Guilai” (ST 29) and “Sanyinjiao” (SP 6) was carried out for 4 weeks. In present study, morphology, 3D imaging, molecular biology and other experimental techniques were used to study the sympathetic nerve and activity of BAT.
Results: First, dihydrotestosterone-induced PCOS-like rats showed both obvious weight gain and reproductive dysfunction, similar to what is seen in high-fat dietinduced obesity rats except for the absence of reproductive dysfunction. We found that the body weight gain was mainly caused by an increase in WAT, but surprisingly we also observed 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. We used tissue clearing and 3D high-resolution imaging technology to show 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: Taken together, the results of our study highlight the significant role of BAT and its sympathetic innervations in PCOS and in EA therapy. Keywords: polycystic ovary syndrome, electroacupuncture, brown adipose tissue, sympathetic nerve, mitochondrial brown fat uncoupling protein 1