Obesity is a metabolic dysfunction triggered by refined carbohydrate and high-fat-rich foods, as well as sedentary lifestyle. It can also be as a result of increased calorie intake and reduced calorie expenditure mediated through environmental, genetic, epigenetic and neuropsychological factors (Castro et al., 2017;Leisegang et al., 2019). It is usually characterised by increased visceral adiposity (Agarwal et al., 2018). Obesity has become an epidemic in recent decades, with millions of people worldwide suffering from the disease. Recent data from the World Health Organization showed that over 1.9 billion adults are either overweight or obese, with 650 million adults typically obese (World Health Organization, 2018).
Background
Polycystic ovarian syndrome (PCOS) is pathogenically characterized with hyperandrogenism and metabolic alterations, which often result in ovarian changes and infertility in women of reproductive age. Epigenetic changes have been linked to the development of PCOS. However, the involvement of epigenetic regulator, histone deacetylase (HDAC) in PCOS-driven ovarian dysfunction is not clear. Howbeit, the present study hypothesized that acetate, an HDAC inhibitor (HDACi) would protect against ovarian dysfunction in experimentally induced PCOS.
Materials and methods
Female Wistar rats weighing 120–150 g were randomly divided into four groups (n = 6). The groups received vehicle, sodium acetate (200 mg/kg), letrozole (1 mg/kg) and letrozole with acetate by oral gavage respectively. The administrations were done daily for 21 days.
Results
The rat model of PCOS had increased body weight and ovarian weight, 1-hr postload glucose and plasma insulin, testosterone and LH/FSH ratio as well as reduced insulin sensitivity and plasma 17-β estradiol and sex hormone binding globulin. This model of PCOS in addition showed a significant increase in plasma and ovarian triglyceride, total cholesterol, TNF-α and HDAC, and ovarian malondialdehyde as well as a significant reduction in ovarian glutathione peroxidase/reduced glutathione and NrF2 with the histology of ovarian tissues showing disrupted morphology with significant increase in the number of degenerated follicles compared with control group. These alterations were however attenuated when treated with HDACi, acetate.
Conclusion
Altogether, the present results suggest that acetate protects ovarian function with evidence of normal growing follicles and enhanced circulating 17-β estradiol by inhibition of HDAC.
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