Endocrine disruptors present in food packages do act as lipid metabolism modulators.

Endocrine-disrupting chemicals (EDCs) may cause several noxious problems to both humans and wildlife and their modulations on energy balance and lipid metabolism are nowadays of great concern. Among environmental EDCs, plasticizers employed in food wrapping materials are very relevant due to their widespread distribution and persistence in the food chain. In the present work we first identify by in silico screening compounds, among the permitted plasticizers for food packaging (EU Regulation, 10/2011), with high predicted affinity for nuclear receptors known to mediate obesogenic effects, such as PPARs, LXR and RXR. The following molecules were therefore chosen for the subsequent studies: the well-known, bisphenol-A, three phthalates (di-isononylphpthalate, DiNP; Di-isodecyl phthalate, DiDP; diethylene glycol dibenzoate, DiGD) and one organophosphorus (tri-m-cresyl phosphate,TmCP).The predicted affinity for the nuclear receptors was then verified in vitro with a luciferase assay: DiNP, DiDP and DiGD were shown to have activity on PPAR α/γ at 10-5-10-7M and to induce the expression of downstream target genes (FABP4, PDK4, FGF21, CPT2). The potential obesogenic effects of the selected compounds were then tested on 3T3-L1 murine preadipocytes cells, a widely used model for adipogenesis in vitro. All the molecules, when used in a range of 10-8-10-6M, were able to significantly enhance lipid droplets deposition, both when administered during the two-days differentiation induction, as well as when maintained for all the eight-days post-differentiation period. Food plastic packages are mostly composed by a mixture of plasticizers so that many molecules at the same time may migrate and contaminate food. We consequently treated 3T3-L1 cells with mixtures of the selected plasticizers (10-8M each), coherently with some commercial plastics (pvc, polypropylene, polyethylene teraphthalate), and we observed in all the cases a significant positive modulation on lipid deposition. The obesogenic effects of the compounds were also investigated by performing qRT-PCR on target genes such as PPARs, LXR, RXR and their downstream effectors. Taken together, our data enforce the emerging awareness on energy balance and lipid metabolism modifications following environmental exposure that could be of concern in vulnerable periods, such as early postnatal life.