PERINATAL EXPOSURE TO BISPHENOL-A DISRUPTS LEPTIN SIGNALING AND INDUCES METABOLIC DYSFUNCTION IN PRE ADOLESCENT WISTAR RATS.

Abstract

Abstract 
Bisphenol A (BPA) is a ubiquitous endocrine disruptor linked to metabolic syndrome. This study investigated the dose-dependent effects of perinatal BPA exposure on leptin levels and metabolic homeostasis in pre-adolescent Wistar rats. Pregnant rats received 
oral BPA at 0, 2.5, 25, or 2500 µg/kg from gestational day 0 to postnatal day (PND) 13. Pups were directly gavaged with the same doses from PND 14 to 28, then euthanized on PND 29. Serum leptin, insulin, glucose, GLP-1, lipids, and oxidative 
stress markers were analyzed. BPA exposure significantly reduced serum leptin levels in a dose-dependent manner (p ≤ 0.05), correlating with increased body weight, particularly at 2500 µg/kg. A non-monotonic response was observed for insulin—
decreasing at lower doses but increasing at 2500 µg/kg—while fasting glucose remained elevated across all BPA groups. Lipid profiles were disrupted: triglycerides increased at 2.5 and 2500 µg/kg, while LDL rose at the highest dose. Conclusion: 
Early-life BPA exposure, even at human-relevant doses, suppresses leptin and impairs glucose and lipid metabolism. These findings suggest that BPA-induced leptin suppression may be a primary driver of metabolic dysfunction, potentially predisposing 
individuals to obesity and metabolic disorders later in life.