Bisphenol A remodels brown adipose tissue via apoptosis, whitening, and inflammatory stress.

Bisphenol A (BPA) exposure may be particularly detrimental to brown adipose tissue (BAT) due to its unique cellular composition, lifelong thermogenic function, and higher BPA accumulation than white adipose tissue, yet the mechanisms by which BPA affects BAT remain unclear. In this study, BPA exposure for six weeks in male mice remodeled the interscapular adipose tissue depot by reducing BAT mass and increasing white adipose tissue, with minimal impact on overall depot weight. The decrease in BAT substantially resulted from increased apoptosis and whitening of brown adipocytes, characterized by enlarged adipocytes with lower nuclear density, decreased mitochondrial DNA content per cell and elevated expression of adipogenic markers, collectively contributing to reduced cellularity. Moreover, BPA induced cytotoxic effects characterized by NF-κB-mediated inflammation, peroxisomal β-oxidation-induced oxidative stress, and cell death through apoptosis and autophagy, all of which contributed to BAT remodeling. These findings highlight key mechanisms of BPA-induced BAT remodeling through whitening, hypertrophy, and cell loss and underscore the need for translational studies to better understand BPA-associated adipose toxicity in humans.