Suppression of adipose TGF-β1 by probiotics alleviates metabolic disturbance in experimentally induced PCOS

Polycystic ovarian syndrome (PCOS) is critically characterized with metabolic and endocrine dysfunctions, precipitating metabolic syndrome and infertility in reproductive aged women. Adipose tissue dysfunction has been implicated in the pathogenesis of metabolic syndrome, including in PCOS individuals. Probiotics are healthy bacteria in the gut that regulate metabolic health. However, the impact of probiotics on adipose-driven metabolic syndrome has not been reported. The present study therefore hypothesized that probiotics would attenuates metabolic disturbance in experimental PCOS rat model, probably by suppression of TGF-β1.

Eight-week-old female Wistar rats were randomly allotted into four groups (n = 5). Administration of letrozole (1 mg/kg p.o) for 21 days induced PCOS, thereafter the animals were treated with 3x10⁹ CFU (p. o) of probiotics for six weeks.

Letrozole-induced PCOS rats were characterized with elevated circulating testosterone, and multiple ovarian cysts. In addition, rats with PCOS developed increased body weight, which was also accompanied with insulin resistance, hyperinsulinemia, and increased leptin, and decreased adiponectin and adipose TG, as well as elevated adipose lipase. Inflammatory markers (NF-kB, TNF-α) were elevated, while antioxidant defense (GSH) was depleted in PCOS animals. A significant increase in adipose TGF-β1, caspase-6 and HDAC2 levels was observed in PCOS rats when compared with the control. Immunohistochemical evaluation of adipose tissue also showed severe expression of NLRP3 in PCOS rats and these changes were accompanied by increased level of TGF-β1. However, treatment with probiotics reversed these aberrant systemic and adipose tissue changes in PCOS model.

The present results suggest the therapeutic benefit of probiotics against metabolic disturbance in PCOS model through suppression of TGF-β1-dependent pathway.