Recent data suggest that endocrine-disrupting chemicals (EDCs) may alter lipid metabolism and energy balance. Among environmental EDCs, plasticizers employed in food packaging are of great concern due to their widespread distribution and high persistency in the food chain. We first selected by in silico screening several compounds from a list of plasticizers approved for food packaging (EU Regulation 10/2011) showing high affinity for lipogenic nuclear receptors (PPARs, LXR and RXR). The following plasticizers were chosen: the well-known bisphenol-A, three phthalates (diisononylphpthalate, DiNP; Di-isodecyl phthalate, DiDP; diethylene glycol dibenzoate, DiGD) and one organophosphorus compound (tri-m-cresylphosphate,TmCP).Their binding capacity to nuclear receptors was verified on HEPG2 cells transfected with receptor-luciferase reporter constructs; all phtalates (10-5-10-7 M) were shown to activate PPAR and to induce the expression of downstream target genes (FABP4, PDK4, FGF21, CPT2). The potential obesogenic effects of these compounds were then tested on differentiating 3T3-L1 preadipocyte cells. All molecules (10-8-10-6 M) were able to significantly enhance lipid droplet deposition when administered both in the two-days differentiation induction, or in the eight-days post differentiation period. Food plastic packaging is mostly composed by mixtures of plasticizers, so multiple molecules may migrate simultaneously into food. We therefore treated 3T3-L1 cells with mixtures of plasticizers (10-8 M each), mimicking commercial plastics (pvc, polypropylene, polyethylene teraphthalate); in all cases we observed a significant positive modulation of lipid deposition. The obesogenic effects of all compounds were also investigated at the molecular level 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 alteration of lipid metabolism following environmental exposure to plasticizers. This effect could be of special concern in vulnerable periods such as pregnancy and early postnatal life.
|Titolo:||Plasticizers present in food packaging significantly affect lipid metabolism|
|Data di pubblicazione:||2014|
|Appare nelle tipologie:||Contributo in atto di convegno su volume|