Accumulation of Polychlorinated Biphenyls in Adipocytes: Selective Targeting to Lipid Droplets and Role of Caveolin-1

Abstract

BackgroundPolychlorinated biphenyls (PCBs) are persistent environmental pollutants that preferentially accumulate in lipid-rich tissues of contaminated organisms. Although the adipose tissue constitutes a major intern reservoir of PCBs and recent epidemiological studies associate PCBs to the development of obesity and its related disorders, little is known about the mechanisms involved in their uptake by the adipose tissue and their intracellular localization in fat cells.Methodology/Principal FindingsWe have examined the intracellular distribution of PCBs in mouse cultured adipocytes and tested the potential involvement of caveolin-1, an abundant adipocyte membrane protein, in the uptake of these compounds by fat cells. We show that 2,4,4′-trichlorobiphenyl (PCB-28), 2,3′,4,4′,5-pentachlorobiphenyl (PCB-118) and 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB-153) congeners rapidly and extensively accumulate in 3T3-L1 or mouse embryonic fibroblast (MEF) derived cultured adipocytes. The dynamics of accumulation differed between the 3 congeners tested. By subcellular fractionation of primary adipocytes, we demonstrate that these pollutants were almost exclusively recovered within the lipid droplet fraction and practically not associated to cell membranes. The absence of caveolin-1 expression in primary adipocytes from cav-1 deficient mice did not modify lipid droplet selective targeting of PCBs. In cav-1 KO MEF differentiated adipocytes, PCB accumulation was decreased, which correlated with reduced cell triglyceride content. Conversely, adenoviral mediated cav-1 overexpressing in 3T3-L1 cells, which had no impact on total cell lipid content, did not change PCB accumulation.Conclusion/SignificanceOur data indicate that caveolin-1 per se is not required for selective PCB accumulation, but rather point out a primary dependence on adipocyte triglyceride content. If the crucial role of lipid droplets in energy homeostasis is considered, the almost exclusive accumulation of PCBs in these organelles warrants future attention as the impairment of their function could be linked to the worldwide obesity epidemic.

Polychlorinated biphenyls (PCB 101, PCB 153 and PCB 180) alter leptin signaling and lipid metabolism in differentiated 3T3-L1 adipocytes

“…These limits are fixed to protect consumer health from exposure to foods containing PCBs. Experimental studies have been mainly performed to evaluate the accumulation dynamics, storage and release in/from adipose cells of NDL-PCBs (Bourez et al, 2012(Bourez et al, , 2013Gallenberg and Vodicnik, 1987).…”

Polychlorinated biphenyls (PCBs) alter DNA methylation and genomic integrity of sheep fetal cells in a simplified in vitro model of pregnancy exposure

“…We observed that fetal fibroblasts and amniocytes responded differently to PCB exposure probably because of their different roles into the organism and their different biological features, such as lipid content. PCBs possess high lipophilic properties (Yu and Mylander, 2011) and can accumulate mainly in cells with high lipid content (Müllerová and Kopecký, 2007;Bourez et al, 2012). In this regard, the literature reveals a lower degree of PCBs accumulation in the amniotic fluids compared to other biological compartments, such as Table 2 Frequency of chromosomal abnormalities in SEF.…”

PCB-153 Shows Different Dynamics of Mobilisation from Differentiated Rat Adipocytes during Lipolysis in Comparison with PCB-28 and PCB-118

“…The PCBs were added to the culture medium as ethanolic solution and four conditions of PCB contamination were tested: ( i ) 2,4,4′-trichlorobiphenyl (PCB-28); ( ii ) 2,3′,4,4′,5-pentachlorobiphenyl (PCB-118); ( iii ) 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB-153); ( iv ) an equimolar mixture of three PCB congeners (PCB-28, -118 and -153), also called cocktail of PCBs. In all conditions of contamination, each PCB was added to the culture medium at a concentration of 300 nM, which is within the range of concentrations found in in vivo and in vitro studies [4], [29], [30]. Impact of the ethanol vehicle was tested earlier [4].…”

“…In all conditions of contamination, each PCB was added to the culture medium at a concentration of 300 nM, which is within the range of concentrations found in in vivo and in vitro studies [4], [29], [30]. Impact of the ethanol vehicle was tested earlier [4].…”