Lipid Homeostasis Perturbation by Organotins: Effects on Vertebrates and Invertebrates
Pp. 83-96 (14)
Miguel Machado Santos, Maria Armanda Reis-Henriques and Luis Filipe Costa Castro
Lipid homeostasis is essential for the maintenance of the organism energy balance while enabling the
cells to perform vital functions. In mammals, improper control of these metabolic pathways can result in serious
health problems, such as obesity, increased risk of coronary artery diseases, diabetes and related problems, such
as hypertension and lipidemia. The nuclear receptor peroxisome proliferator-activated receptorγ (PPARγ),
together with its heterodimeric partner retinoid X receptor (RXR), is a master regulator of adipocyte
differentiation, being involved in the regulation of food intake, metabolic efficiency and energy storage.
Triorganotins such as tributyltin (TBT) and triphenyltin (TPhT) are high affinity ligands of both RXRs and
PPARγ. In line with these findings, the use of the 3T3-L1 cell system, a well characterized model for
adipogenesis, demonstrated that organotins stimulate 3T3-L1 cells differentiation and the expression of adipocyte
marker genes. In vivo exposure of neonate mice to TBT significantly elevates lipid accumulation in several
tissues, thus supporting the hypothesis that chronic lifetime human exposure to organotins may increase the risk
of obesity. While PPAR has not been described outside deuterostomes, RXR is ubiquitous within metazoans.
Thus, the taxonomic scope for organotin-mediated lipid homeostasis disruption may be wider than initially
anticipated. This is further supported by the observation of increased lipid accumulation in amphibians and teleost
fish and changes to the lipid profile in molluscs after organotin exposure. Therefore, we review here the current
evidence on the molecular and biochemical mechanisms for organotin-mediated lipid homeostasis disruption
within several metazoan phyla.
Nuclear receptors - endocrine disruption - adipogenesis - lipogenesis-obesity - invertebrates -
CIMAR/CIIMAR, Interdisciplinary Centre of Marine and Environmental Research, Laboratory of Environmental Toxicology, University of Porto, Rua dos Bragas 289, 4050-123 Porto, Portugal.