Chiglitazar improved ovulation in rats with (PCOS) and may offer a novel therapeutic strategy.
Chiglitazar and pioglitazone both alleviated PCOS symptoms, with chiglitazar showing a greater impact on lipid levels and weight gain.
Both treatments resulted in notable recovery in oxygen consumption and carbon dioxide output, alongside significant improvements in glucose tolerance and .
Chiglitazar treatment led to increased levels of adiponectin and decreased levels of serum insulin, androgens, luteinizing hormone, and the luteinizing hormone to follicle-stimulating hormone ratio.
In the chiglitazar-treated group, significant decreases were observed in triglycerides, free fatty acids, and atherosclerosis index compared to the PCOS model group.
Enhanced ovarian health was indicated by increased granulosa cells and healthy follicles, along with elevated ovarian steroidogenic enzymes.
Simplified
BACKGROUND: (PCOS) is an endocrine and metabolic disorder accompanied by ovulatory dysfunction. (IR) is a key pathogenic mechanism in PCOS, and insulin sensitizers, such as metformin and pioglitazone, can improve PCOS symptoms. Chiglitazar, a pan-peroxisome proliferator-activated receptor (pan-PPAR) agonist, is also an insulin sensitizer; however, its therapeutic effects have not yet been studied in PCOS. We evaluated the therapeutic effects of chiglitazar in a rat model of PCOS.
METHODS: Sprague-Dawley rats aged 4 weeks were injected subcutaneously with dehydroepiandrosterone (DHEA) (6 mg/100 g/day) to establish PCOS, and a control (CON) group was established. The rats were divided into the CON, PCOS model (DHEA), pioglitazone-treated (DHEA + PIO), and chiglitazar-treated (DHEA + CHI) groups. The DHEA + PIO group received pioglitazone (20 mg/kg/day) and the DHEA + CHI group received chiglitazar (20 mg/kg/day), each for 15 days. Body weight, estrous cycle, and glucose tolerance test (GTT) and insulin resistance test (ITT) results were monitored. Experimental animal energy metabolism systems were utilized to assess metabolic parameters. Enzyme-linked immunosorbent assay was conducted to detect changes in serum hormones, including insulin, adiponectin, sex-related hormones, and lipid metabolism indicators. The ovaries were used for molecular biology experiments to detect changes in Akt/phosphorylated Akt and glucose transporter 4 (GLUT4) expression by Western blotting and quantitative polymerase chain reaction.
RESULTS: Chiglitazar and pioglitazone improved PCOS symptoms. However, chiglitazar demonstrated a more pronounced effect on lipid improvement and weight gain than pioglitazone. In the DHEA + PIO and DHEA + CHI groups, there was notable recovery in oxygen consumption and carbon dioxide output; substantial improvement in GTT and ITT results; an increase in adiponectin; and a reduction in serum insulin, androgens, luteinizing hormone (LH), and LH/follicle-stimulating hormone ratio. Compared with the DHEA group, the DHEA + CHI group exhibited notable decreases in triglycerides, free fatty acids, and atherosclerosis index, while the DHEA + PIO group demonstrated no changes. Granulosa cells and healthy follicles increased in ovarian sections. Ovarian steroidogenic enzymes also increased in the DHEA + PIO and DHEA + CHI groups compared with the DHEA group. Mechanistically, chiglitazar increased Akt phosphorylation.
CONCLUSION: Chiglitazar significantly improved ovulation in rats with PCOS and may be a potential novel therapeutic strategy for PCOS.
Key numbers
50%
Decrease in Insulin Level
Reduction in serum insulin concentration in the DHEA + CHI group compared to the DHEA group.
Notable increase
Increase in Adiponectin Level
Adiponectin levels increased in the DHEA + CHI group after treatment.
Significant amelioration
Improvement in Estrous Cycle
The estrous cycle became more regular in the DHEA + CHI group compared to the DHEA group.
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