Luteolin Treats Obese Rats With Polycystic Ovary Syndrome by Improving Liver Lipid Metabolism and Regulating the Gut Microbiota

ABSTRACT Polycystic ovary syndrome (PCOS) and obesity share a bidirectional relationship. While previous studies have indicated the anti‐obesity effects of luteolin, its role in PCOS exacerbated by obesity remains unclear. This study aimed to investigate the ameliorative effects of luteolin on obese rats with PCOS and explore its underlying mechanisms. We established a rat model of PCOS with obesity and administered luteolin to evaluate its mitigating effects on the metabolic phenotype. Liver transcriptomics and fecal metagenomics were employed to analyze potential targets and alterations in the gut microbiota composition associated with luteolin's effects. Results showed that luteolin reduced body weight, improved estrous cycles, polycystic ovarian morphology, and glucose tolerance, and lowered serum levels of triglycerides (TG), total cholesterol (TC), and low‐density lipoprotein cholesterol (LDL‐c) in the model rats. Importantly, luteolin significantly alleviated hepatic steatosis and reversed the expression of 138 key differentially expressed genes (DEGs) in the liver, including UQCRC2, IRS2, NFIX, and ALDH6A1. In addition, luteolin significantly increased the alpha diversity of the gut microbiota and modulated its composition, specifically increasing the relative abundance of Bacteroidota and decreasing that of Firmicutes . Our findings suggest that luteolin exerts beneficial effects on PCOS with obesity, potentially mediated through the improvement of hepatic lipid metabolism and the restoration of gut microbiota homeostasis. Luteolin emerges as a promising therapeutic candidate for managing PCOS with obesity.