Non-dioxin-like polychlorinated biphenyls (PCB 101, 153, and 180) and adipocyte lipid dysfunctions: Involvement of glycerol and role of aquaglyceroporins in mature 3T3-L1 cells.

Non-dioxin-like polychlorinated biphenyls (NDL-PCBs), as well as dioxin-like PCBs, are endocrine disruptors that persist in human and animal tissues worldwide. Due to their lipophilicity and resistance to enzymatic degradation, PCBs accumulate in fat deposits contributing to the onset of endocrine and metabolic diseases. Aquaporins (AQPs) are transmembrane channel proteins that allow the transport of water and small solutes. In particular, the aquaglyceroporins AQP3, AQP7, and AQP9 mediate the release and the uptake of glycerol in adipose tissue. Here, we investigate the modulation of these AQPs by NDL-PCBs and the following effects on lipid metabolism in mature 3T3-L1 adipocytes exposed for 48 h to PCB 101, 153, or 180 (1 μM). NDL-PCBs modulated protein expression of AQP3 and AQP7, involved in glycerol release, and AQP9, implicated in glycerol uptake. This modulation induced a greater accumulation of glycerol in treated adipocytes indirectly evaluated by its reduction in the culture media. Interestingly, only PCB 153 altered the expression of enzymes involved in glycerol metabolism and lipid accumulation (i.e. Pparg, Fabp4, Gyk, Dgat1, and Agpat9). These modifications indicated an increase of adipocyte lipid accumulation confirmed by Oil Red O staining. The role of AQPs in the increased cellular accumulation of glycerol was confirmed using phloretin, an AQP9 inhibitor, that reverted the PCB 153 effect. Our results show the involvement of AQPs in PCB 153-induced dysfunction of glycerol metabolism and lipid storage in adipocytes, contributing to better defining the mechanisms underlying its known obesogenic effect.