Eicosatrienoic acid improves PCOS in mice by modulating the intestinal barrier and ovarian inflammation

Polycystic ovary syndrome (PCOS) is a prevalent metabolic and endocrine disorder marked by hormonal imbalances among women, and the specific pathogenesis remains incompletely clarified. Although n-3 polyunsaturated fatty acids (n-3 PUFAs) have been shown to have benefits in managing PCOS through previous studies, the specific mechanisms require further investigation. We found that DHEA-induced PCOS mice exhibited an impaired intestinal barrier, decreased levels of glucagon-like peptide-1 (GLP-1, P<.05), elevated serum levels of lipopolysaccharides (LPS, P<.05), and upregulated the ovarian TLR4-NLRP3 inflammatory signaling pathway (P<.05). Our in-depth experiments verified that eicosatrienoic acid (ETA) palliated the pathological representative features of PCOS in mice by regulating intestinal GLP-1 levels (P<.01). In detail, ETA upregulated GLP-1 receptor (GLP-1R) levels in the colon, restoring intestinal barrier integrity through modulation of the functions of the gut epithelial and mucosal barriers, and reduced serum LPS levels in PCOS mice (P<.001). In the ovary, ETA upregulated GLP-1R levels, decreased the expression of the TLR4-NLRP3 signaling pathway (P<.05), and reduced the release of inflammatory factors (all P<.05), thereby ameliorating ovarian inflammation and estradiol secretion disorders (P<.01). Here, we propose the mitigation of ovarian inflammation and restoration of intestinal barrier integrity as novel therapeutic targets and strategies for PCOS management, thereby positioning the n-3 PUFA ETA as a promising therapeutic candidate.