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

Ana Paula de Paula Alves ¹, Emanuelle Barreto-Reis ², Beatriz Gouvêa de Luca ³

¹Research Center on Morphology and Metabolism, Biomedical Institute, Fluminense Federal University, Niteroi, RJ, Brazil; Laboratory of Experimental Endocrinology, Institute of Biomedical Science, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Endocrinology Graduate Program, Faculty of Medicine, Federal University of Rio de Janeiro, Brazil; National Institute of Endocrine Disruptors and Endocrine-Metabolic Repercussions, Brazil.
²Research Center on Morphology and Metabolism, Biomedical Institute, Fluminense Federal University, Niteroi, RJ, Brazil; Pathology Graduate Program, Fluminense Federal University, Niteroi, RJ, Brazil; National Institute of Endocrine Disruptors and Endocrine-Metabolic Repercussions, Brazil.
³Pathology Graduate Program, Fluminense Federal University, Niteroi, RJ, Brazil; Laboratory of Teaching and Research in Histology and Comparative Embryology, Fluminense Federal University, Niteroi, RJ, Brazil; National Institute of Endocrine Disruptors and Endocrine-Metabolic Repercussions, Brazil.
⁴Research Center on Morphology and Metabolism, Biomedical Institute, Fluminense Federal University, Niteroi, RJ, Brazil; Sciences and Biotechnology Graduate Program, Fluminense Federal University, Niterofi, RJ, Brazil; National Institute of Endocrine Disruptors and Endocrine-Metabolic Repercussions, Brazil.
⁵Research Center on Morphology and Metabolism, Biomedical Institute, Fluminense Federal University, Niteroi, RJ, Brazil; National Institute of Endocrine Disruptors and Endocrine-Metabolic Repercussions, Brazil.
⁶Research Center on Morphology and Metabolism, Biomedical Institute, Fluminense Federal University, Niteroi, RJ, Brazil; Laboratory of Exercise Sciences, Fluminense Federal University, Niteroi, RJ, Brazil.
⁷Pathology Graduate Program, Fluminense Federal University, Niteroi, RJ, Brazil; National Institute of Endocrine Disruptors and Endocrine-Metabolic Repercussions, Brazil.
⁸Laboratory of Teaching and Research in Histology and Comparative Embryology, Fluminense Federal University, Niteroi, RJ, Brazil.
⁹Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro (UFRJ), Brazil; National Institute of Endocrine Disruptors and Endocrine-Metabolic Repercussions, Brazil.
¹⁰Laboratory of Experimental Endocrinology, Institute of Biomedical Science, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Endocrinology Graduate Program, Faculty of Medicine, Federal University of Rio de Janeiro, Brazil; Pharmacology and Medicinal Chemistry Graduate Program, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Brazil; Morphological Sciences Graduate Program, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Brazil; National Institute of Endocrine Disruptors and Endocrine-Metabolic Repercussions, Brazil.
¹¹Research Center on Morphology and Metabolism, Biomedical Institute, Fluminense Federal University, Niteroi, RJ, Brazil; Laboratory of Experimental Endocrinology, Institute of Biomedical Science, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Endocrinology Graduate Program, Faculty of Medicine, Federal University of Rio de Janeiro, Brazil; Sciences and Biotechnology Graduate Program, Fluminense Federal University, Niterofi, RJ, Brazil; National Institute of Endocrine Disruptors and Endocrine-Metabolic Repercussions, Brazil.

⁰Research Center on Morphology and Metabolism, Biomedical Institute, Fluminense Federal University, Niteroi, RJ, Brazil; Laboratory of Experimental Endocrinology, Institute of Biomedical Science, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Endocrinology Graduate Program, Faculty of Medicine, Federal University of Rio de Janeiro, Brazil; National Institute of Endocrine Disruptors and Endocrine-Metabolic Repercussions, Brazil.

Molecular and Cellular Endocrinology +

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October 19, 2025

View abstract on PubMed

Summary

Bisphenol S (BPS) exposure causes obesity and metabolic changes, impacting pancreas and white adipose tissue (WAT). Even low doses of BPS, with or without a high-fat diet, promote obesogenic effects and worsen insulin resistance.

Area Of Science

Endocrinology
Metabolic disease
Toxicology

Background

Obesity is a chronic inflammatory disease with multiple comorbidities.
Bisphenol S (BPS), a substitute for Bisphenol A (BPA), is an endocrine disruptor.
BPS may affect pancreas and white adipose tissue (WAT) morphology and metabolism.

Purpose Of The Study

To investigate the obesogenic effects of BPS, alone or with a high-fat diet (HF).
To examine the impact of BPS on pancreas and epididymal WAT (eWAT) morphology and metabolism.

Main Methods

Male C57BL/6 mice were divided into four groups: standard chow (SC), SC + BPS (SCB), HF diet (HF), and HF + BPS (HFB).
BPS was administered at 25 μg/kg/day via drinking water for 12 weeks.
Analyses included body mass, tissue weights, plasma parameters, insulin resistance, morphometry, stereology, eWAT mRNA, and ER stress markers.

Main Results

All interventions increased body mass, pancreatic islet size, adipocyte size, and levels of insulin, glucose, and cholesterol.
BPS and HF diet increased ER stress markers (GRP78, ERO1, ATF4) and inflammatory markers.
Combined BPS and HF diet exacerbated insulin resistance and increased triacylglycerol levels.

Conclusions

BPS exhibits obesogenic activity, independently affecting metabolism and remodeling pancreatic islets and eWAT.
BPS exposure, even at low doses, can lead to adverse metabolic and morphological changes.
BPS poses a risk for metabolic dysfunction and obesity, particularly when combined with a high-fat diet.

Keywords:

Bisphenol S Metabolism Obesity Pancreas White adipose tissue

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