Endocrine Abstracts

Background: Polycystic ovary syndrome (PCOS) is a complex reproductive event that is delineated by endocrine and metabolic disorders. Alteration of kisspeptin status in the hypothalamus and adipose tissue is critical to increased endocrine/metabolic derangements in PCOS individuals, aggravating the clinical manifestation of PCOS and its complications. Short chain fatty acids (SCFAs) are crucial modulators of metabolic homeostasis. However, the role of SCFAs, in particular, acetate on hypothalamic-adipose kisspeptin status (HAKS) in PCOS model is unknown. The present study hypothesized acetate as a key player in restoration of deranged HAKS associated with experimental rat model of PCOS.

Materials and Methods: Three groups (n=6/group) of female Wistar rats (8 weeks old) were used. The groups were treated (po) for 21 days with vehicle, letrozole (1 mg/kg) with or without acetate (200 mg/kg) respectively.

Results: Animals that received letrozole only had impaired glucose homeostasis, elevated testosterone/leptin and LH/FSH ratio and decreased GnRH/adiponectin with ovarian tissues largely characterized with degenerated follicles and disrupted morphology. In addition, these animals also showed increased hypothalamic lipid and decreased adipose lipid with a corresponding increase in hypothalamic/adipose malondialdehyde, NF-κB/TNF-α and decreased GSH/G6PD and hypothalamic but not adipose kisspeptin. Immunohistochemical analysis revealed the expression of inflammasome (NLRP3) and PROKR1 in the hypothalamic and adipose tissue. Altogether, the present results demonstrate that PCOS is characterized with hypothalamic-adipose inflammation, accompanied by immunohistochemical expression of NLRP3/PROKR1 with consequent alteration of hypothalamic but not adipose kisspeptin.