Dingkun pill alleviates metabolic abnormalities in polycystic ovary syndrome through brown adipose tissue activation

Abstract

Abstract Background Traditional Chinese medicine has been used for a long time to treat a variety of gynecological diseases. Among various traditional Chinese medicine, Dingkun Pill (DK) has been used for the treatment of female gynecological diseases. However, DK therapeutic effect on PCOS and the target tissue for its potential effect need to be explored. This study aims to explore the therapeutic effect of DK for PCOS in mice from three aspects: metabolism, endocrine and fertility, and determine whether the brown adipose tissue is the target organ to alleviate the PCOS phenotype. Methods PCOS mouse model was constructed by subcutaneous injection of DHEA. The estrous cycle, ovulation, and pregnancy outcome was examined in mice. The level of hormone including the LH, FSH, estrogen and testosterone in the serum were measured by ELISA. Both the glucose sensitivity and insulin sensitivity were determined in mice with different treatment. The histomorphology and lipid contents in the brown adipose tissue were analyzed. RNA-Seq was conducted for the brown adipose tissue and different expression of critical metabolism marker genes was confirmed by real-time PCR. Results The data showed that the fertility in PCOS mice with DK treatment was significantly increased, and the metabolic disorder was partially restored. Both the whiten of brown adipose tissue and reduced UCP1 expression induced by DHEA was rescued by the DK. The RNA-Seq data further demonstrated both the DHEA induced downregulation of lipolysis genes and oxidative phosphorylation genes were at least partially rescued by DK in the brown adipose tissue. Conclusions DK has therapeutic effect on PCOS in DHEA treated mice and the brown adipose tissue is at least one critical target organ to alleviate the PCOS. This is achieved by not only regulating the lipid mobilization of brown adipose, but also restoring its thermogenic function.