Bisphenol S chronic exposure impairs pancreatic function and induces obesity in male mice independently of high-fat diet intake.

Obesity is a chronic inflammatory disease linked to several comorbidities. Bisphenol S (BPS), a BPA substitute, is an endocrine disruptor that may impact pancreas and white adipose tissue (WAT) morphology and metabolism. This study investigated the obesogenic effects of BPS, alone or with a high-fat diet (HF), on pancreas and epididymal WAT (eWAT) morphology. Male C57BL/6 mice (n = 12) were divided into four groups: standard chow (SC), standard chow + BPS (SCB), HF diet (HF), and HF diet + BPS (HFB). BPS exposure (25 μg/kg/day) occurred via drinking water for 12 weeks. Body mass, pancreas and eWAT weights, plasma parameters, insulin resistance, morphometry, stereology, eWAT mRNA levels and protein expression of ER stress markers were analyzed. All interventions increased body and tissue masses, pancreatic α-cells and β-cells, Pparγ mRNA level, GRP78, ERO1 and ATF4 protein expression, epididymal adipocyte size, and insulin, glucose, and cholesterol levels. HF and HFB groups also showed increased Grp78 mRNA level, p-eIF2α and CHOP expression, pancreatic islet diameter, inflammatory infiltrate, and triacylglycerol levels. BPS combined with HF diet worsened insulin resistance. These findings suggest that BPS has obesogenic activity, affecting metabolism and remodeling pancreatic islets and eWAT, even at low doses, independently of a HF diet.