Sildenafil ameliorates leptin resistance and normalizes lipid handling in the hypothalamic and adipose tissues of testosterone-exposed pregnant rats
Emmanuel Damilare Areola,
Isaiah Woru Sabinari,
Taofeek Olumayowa Usman,
Faith Ifeoluwa Abayomi,
Onyeka Onyezia,
Bisola Onaolapo,
Phebe Oluwaseun Adetokunbo,
Olympus Oyewole Adebanjo,
Funmilayo Rebecca Oladipupo,
Lawrence Aderemi Olatunji
Affiliations
Emmanuel Damilare Areola
HOPE Cardiometabolic Research Team and Department of Physiology, College of Health Sciences, University of Ilorin, Nigeria
Isaiah Woru Sabinari
HOPE Cardiometabolic Research Team and Department of Physiology, College of Health Sciences, University of Ilorin, Nigeria
Taofeek Olumayowa Usman
HOPE Cardiometabolic Research Team and Department of Physiology, College of Health Sciences, University of Ilorin, Nigeria; Cardiovascular Unit, Department of Physiology, College of Health Sciences, Osun State University, Osogbo, Nigeria
Faith Ifeoluwa Abayomi
HOPE Cardiometabolic Research Team and Department of Physiology, College of Health Sciences, University of Ilorin, Nigeria
Onyeka Onyezia
HOPE Cardiometabolic Research Team and Department of Physiology, College of Health Sciences, University of Ilorin, Nigeria
Bisola Onaolapo
HOPE Cardiometabolic Research Team and Department of Physiology, College of Health Sciences, University of Ilorin, Nigeria
Phebe Oluwaseun Adetokunbo
HOPE Cardiometabolic Research Team and Department of Physiology, College of Health Sciences, University of Ilorin, Nigeria
Olympus Oyewole Adebanjo
HOPE Cardiometabolic Research Team and Department of Physiology, College of Health Sciences, University of Ilorin, Nigeria
Funmilayo Rebecca Oladipupo
HOPE Cardiometabolic Research Team and Department of Physiology, College of Health Sciences, University of Ilorin, Nigeria
Lawrence Aderemi Olatunji
HOPE Cardiometabolic Research Team and Department of Physiology, College of Health Sciences, University of Ilorin, Nigeria; Corresponding author.
Leptin and hypothalamic-adipose lipid handling are relevant in determining the shift of metabolic activities. There are scanty findings connecting glucose dysregulation as a result of hyperandrogenism during gestation to hypothalamic-adipose axis and leptin resistance. Sildenafil has recently gained attention in the prevention of intra-uterine growth restriction. The present study aimed at demonstrating the effect of sildenafil on leptin resistance and hypothalamic-adipose lipid handling in testosterone-exposed pregnant rats. Three groups of pregnant Wistar rats (n = 5/group) received olive oil (Ctr, S.C.) or testosterone propionate (Tes, 3.0 mg/kg; sc)or testosterone propionate (3.0 mg/kg; sc) and sildenafil (Tes + PDE5, 50 mg/kg; po)from gestational day 14–19. Blood samples, hypothalamus and adipose tissue were excised for biochemical analysis on day 20. Adipose and body weights, plasma leptin and adiponectin, adipose and hypothalamic leptin and triglyceride, adipose uric acid, hypothalamic Nrf2, catalase and nitric oxide were reduced following gestational testosterone exposure. Also, fasting insulin, plasma triglyceride, uric acid, leptin-adiponectin ratio, hypothalamic free fatty acid, total cholesterol, uric acid, aspartate transaminase and cyclic guanine monophosphate were elevated by testosterone exposure to pregnant animals. Sildenafil ameliorated leptin resistance and normalized hypothalamic-adipose lipid handling. Therefore, sildenafil protects against testosterone-induced leptin resistance and adverse hypothalamic-adipose lipid handling in pregnant rats.
