Effects of tributyltin as an obesogen chemical on mammalian adipose tissue

Tributyltin (TBT) is an endocrine-disrupting chemical (EDC) with well-established obesogenic properties, promoting adipogenesis and disrupting metabolic homeostasis, thereby contributing to obesity. Owing to its high lipophilicity, TBT readily bioaccumulates through aquatic and terrestrial food chains. Because of these physicochemical characteristics and its environmental persistence, TBT remains detectable worldwide, despite the global ban on its use in antifouling paints implemented in 2008. The obesogenic activity of TBT is primarily mediated through the activation of peroxisome proliferator-activated receptor gamma (PPARγ) and retinoid X receptor (RXR), key regulators of adipocyte differentiation and lipid metabolism. This review includes original research articles focusing on the effects of TBT on adipose tissue. Evidence indicates that TBT induces upregulation of adipogenic markers in white adipose tissue (WAT), impairs thermogenic capacity in brown adipose tissue (BAT), and suppresses the browning process of WAT. Additionally, TBT modulates estrogen-responsive gene expression in pink adipose tissue (PAT). Notably, these effects have been reported at environmentally relevant, low-dose exposures, underscoring TBT as persistent public health concern and highlighting the need for further epidemiological studies and investigations of human exposure. This review integrates evidence from in vitro models, in vivo mammalian studies, and human data, and identifies critical gaps in the current literature, proposing future research directions to elucidate the molecular mechanisms underlying TBT-induced toxicity in adipose tissues.