Abstract
BACKGROUND: Polycystic ovary syndrome (PCOS), a prevalent endocrine disorder, is characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. In light of the critical role of bile acids in metabolic regulation and the therapeutic potential of acupuncture for endocrine-metabolic disorders, this study aims to explore the effects of acupuncture on bile acid metabolism and insulin sensitivity in both PCOS patients and rat models. METHODS: 33 PCOS participants and 28 age/BMI-matched controls were enrolled in a clinical trial (NCT04193371). PCOS participants received 4 month acupuncture plus lifestyle (A&L) or a sham acupuncture plus lifestyle (SA&L) intervention followed by 4 month observation. Serum bile acids were profiled by LC-MS/MS. Multiple hormones and inflammatory markers were analyzed by enzyme-linked immunosorbent assay and insulin sensitivity was evaluated through oral glucose tolerance test and insulin tolerance test. A dihydrotestosterone -induced PCOS rat model was established and treated with acupuncture. The estrous cycle and ovarian morphology were assessed using HE staining, insulin resistance was evaluated and hormone levels were measured. Transcriptome profiling of hepatic tissues was conducted in a PCOS rat model to delineate molecular alterations associated with acupuncture intervention, with particular emphasis on genes involved in bile acid biosynthesis. RESULTS: The homeostasis assessment of insulin resistance (HbA1c, HOMA, AUC) of PCOS is significantly reduced after acupuncture compared to the pre-intervention (p < 0.05). Surprisingly, simultaneously ameliorated outcomes included the body mass index (BMI), sex hormone-binding globulin (SHBG), free androgen index (FAI) and anti-Müllerian hormone (AMH). The potency lasted for another 4 months, indicating the enduring effects of the acupuncture regimen. Metabolic improvements were associated with changes in specific bile acids (e.g., taurocholic acid, lithocholic acid). In PCOS rat models, acupuncture restored regular estrous cycles, reduced the incidence of ovarian cysts and improved the insulin resistant. Transcriptomic analysis of rat liver revealed that acupuncture significantly reversed the expression of genes associated with bile acid metabolism and the FXR signaling pathway. CONCLUSIONS: Acupuncture therapy offers potential therapeutic benefits to PCOS women, with mechanisms involving the bile acid-FXR axis potentially contributing to improvements in insulin resistance and other disease-related symptoms.