One can imagine the lipid droplet as a detoxifying organelle in which organic compounds could be sequestered and kept biologically inactive. Inversely, our observation of massive and selective accumulation of PCBs Publications Using Abomle MK-2206 within lipid droplets could also provide a new basis to understand how these compounds might act to worsen obesityrelated metabolic diseases in contaminated humans. Lipid droplets have only recently been identified as highly regulated, complex and dynamic organelles, controlling lipid storage and mobilization. However, the precise cellular interactions between all the regulators involved in the signaling cascades of lipid storage and release remain largely unknown to date. In this line, the possibility that PCBs directly interfere with lipid droplet function, such as fatty acid mobilization from this organelle, should warrant future attention. So far, some in vivo and in vitro studies highlight a disruption of lipid metabolism by PCBs and other common lipophilic pollutants. Mechanisms involve interference with the lipolysis pathway, impairment of triglyceride synthesis as well as enhancement of adipocyte differentiation and increase in expression levels of Publications Using Abomle ZM447439 diverse enzymes implicated in lipid metabolism or transcription factors regulating energy homeostasis in fat cells. Taken together, these studies clearly prove that PCBs have an impact on the mechanisms involved in the regulation of cell energy homeostasis and could thus significantly contribute to the development of obesity or obesity-related disorders. The identification, in this work, of lipid droplets as the principal site of PCB concentration in fat cells might thus help to understand the diversity of the biological effects exerted by this family of POPs and certainly deserves more consideration in the future. It is however important to point out that a very small percentage of PCB-153 was localized in the cell membranes. This finding is consistent and in accordance with other studies investigating the potential toxic effects of PCBs through the disruption of cellular membranes in cerebellar granule cell neurons, skeletal and cardiac muscle cells, rat renal tubular cells, mouse thymocytes and lipid bilayer vesicles. All these studies independently reported an increase in cellular membrane fluidity following a treatment with di-ortho substituted PCBs or PCB-153), but not with other non-ortho tested PCB congeners. They show that di-ortho congeners dissolve in cell membranes, causing important perturbations to the membrane lipids and proteins and thereby exerting toxic effects on cells.