Kehinde S Olaniyi1, Stephanie E Areloegbe2, Mosunmola B Oyeleke2. 1. Cardio/Repro-metabolic and Microbiome Research Unit, Department of Physiology, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, 360101, Nigeria. olaniyisk@abuad.edu.ng. 2. Cardio/Repro-metabolic and Microbiome Research Unit, Department of Physiology, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, 360101, Nigeria.
Abstract
PURPOSE: Polycystic ovary syndrome (PCOS) is a complex reproductive event that is delineated by endocrine/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, particularly 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 PCOS model. METHODS: Three groups (n = 6/group) of female Wistar rats (120-150 g) were used. The groups were treated (po) for 21 days with vehicle, letrozole (1 mg/kg) with/without acetate (200 mg/kg) respectively. RESULTS: Letrozole-treated animals had impaired glucose homeostasis, elevated testosterone, leptin and LH/FSH ratio and decreased GnRH and adiponectin with ovarian tissues revealing degenerated follicles and disrupted morphology. These animals also showed increased concentration of hypothalamic triglyceride (TG)/total cholesterol (TC), free fatty acid (FFA), and decreased concentration of TG/TC/FFA in visceral adipose tissue (VAT) with an increase in hypothalamic and VAT malondialdehyde, NF-κB/TNF-α and decreased glutathione/G6PD and hypothalamic but not VAT kisspeptin. Immunohistochemical analysis revealed the expression of NLRP3 inflammasome in the hypothalamus and VAT and all these changes were attenuated by acetate. CONCLUSIONS: Altogether, the present results demonstrate that PCOS is characterized with hypothalamic-adipose inflammation, associated with immunohistochemical expression of NLRP3 with significant alteration of hypothalamic but not adipose kisspeptin. The results suggest that acetate restores kisspeptin status in PCOS animals. This beneficial effect is accompanied by repressed NLRP3 immunoreactivity.
PURPOSE: Polycystic ovary syndrome (PCOS) is a complex reproductive event that is delineated by endocrine/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, particularly 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 PCOS model. METHODS: Three groups (n = 6/group) of female Wistar rats (120-150 g) were used. The groups were treated (po) for 21 days with vehicle, letrozole (1 mg/kg) with/without acetate (200 mg/kg) respectively. RESULTS: Letrozole-treated animals had impaired glucose homeostasis, elevated testosterone, leptin and LH/FSH ratio and decreased GnRH and adiponectin with ovarian tissues revealing degenerated follicles and disrupted morphology. These animals also showed increased concentration of hypothalamic triglyceride (TG)/total cholesterol (TC), free fatty acid (FFA), and decreased concentration of TG/TC/FFA in visceral adipose tissue (VAT) with an increase in hypothalamic and VAT malondialdehyde, NF-κB/TNF-α and decreased glutathione/G6PD and hypothalamic but not VAT kisspeptin. Immunohistochemical analysis revealed the expression of NLRP3 inflammasome in the hypothalamus and VAT and all these changes were attenuated by acetate. CONCLUSIONS: Altogether, the present results demonstrate that PCOS is characterized with hypothalamic-adipose inflammation, associated with immunohistochemical expression of NLRP3 with significant alteration of hypothalamic but not adipose kisspeptin. The results suggest that acetate restores kisspeptin status in PCOS animals. This beneficial effect is accompanied by repressed NLRP3 immunoreactivity.
Authors: Adam H Balen; Lara C Morley; Marie Misso; Stephen Franks; Richard S Legro; Chandrika N Wijeyaratne; Elisabet Stener-Victorin; Bart C J M Fauser; Robert J Norman; Helena Teede Journal: Hum Reprod Update Date: 2016-08-10 Impact factor: 15.610