Polychlorinated biphenyls (PCB 101, PCB 153 and PCB 180) alter leptin signaling and lipid metabolism in differentiated 3T3-L1 adipocytes.
Non-dioxin-like polychlorinated biphenyls (NDL-PCBs) are highly lipophilic environmental contaminants that accumulate in lipid-rich tissues, such as adipose tissue. Here, we reported the effects induced by PCBs 101, 153 and 180, three of the six NDL-PCBs defined as indicators, on mature 3T3-L1 adipocytes. We observed an increase in lipid content, in leptin gene expression and a reduction of leptin receptor expression and signaling, when cells were exposed to PCBs, alone or in combination. These modifications were consistent with the occurrence of "leptin-resistance" in adipose tissue, a typical metabolic alteration related to obesity. Therefore, we investigated how PCBs affect the expression of pivotal proteins involved in the signaling of leptin receptor. We evaluated the PCB effect on the intracellular pathway JAK/STAT, determining the phosphorylation of STAT3, a downstream activator of the transcription of leptin gene targets, and the expression of SOCS3 and PTP1B, two important regulators of leptin resistance. In particular, PCBs 153 and 180 or all PCB combinations induced a significant reduction in pSTAT3/STAT3 ratio and an increase in PTP1B and SOCS3, evidencing an additive effect. The impairment of leptin signaling was associated with the reduction of AMPK/ACC pathway activation, leading to the increase in lipid content. These pollutants were also able to increase the transcription of inflammatory cytokines (IL-6 and TNFα). It is worthy to note that the PCB concentrations used are comparable to levels detectable in human adipose tissue. Our data strongly support the hypothesis that NDL-PCBs may interfere with the lipid metabolism contributing to the development of obesity and related diseases.
['Ferrante|Maria C|MC|', 'Amero|Paola|P|', 'Santoro|Anna|A|', 'Monnolo|Anna|A|', 'Simeoli|Raffaele|R|', 'Di Guida|Francesca|F|', 'Mattace Raso|Giuseppina|G|', 'Meli|Rosaria|R|']
D041721:3T3-L1 Cells D017667:Adipocytes D000818:Animals D001391:Azo Compounds D015153:Blotting, Western D002454:Cell Differentiation D004396:Coloring Agents D004785:Environmental Pollutants D015850:Interleukin-6 D020738:Leptin D050356:Lipid Metabolism D051379:Mice D020928:Mitogen-Activated Protein Kinases D011078:Polychlorinated Biphenyls D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 D060888:Real-Time Polymerase Chain Reaction D054411:Receptors, Leptin D050796:STAT3 Transcription Factor D015398:Signal Transduction D000071223:Suppressor of Cytokine Signaling 3 Protein D050826:Suppressor of Cytokine Signaling Proteins D014409:Tumor Necrosis Factor-alpha
Non-dioxin-like polychlorinated biphenyls Leptin receptor AMPK/ACC pathway Pro-inflammatory cytokines Signal transducer and activator of transcription 3