title: Polychlorinated biphenyls (PCB 101, PCB 153 and PCB 180) alter leptin signaling and lipid metabolism in differentiated 3T3-L1 adipocytes.
abstract: 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.
authors: Department of Veterinary Medicine and Animal Productions, Federico II University of Naples, Via Delpino 1, 80137 Naples, Italy.
authors: Maria C
authors: MC
authors: Ferrante
authors: Department of Pharmacy, Federico II University of Naples, Via Montesano 49, 80131 Naples, Italy.
authors: Paola
authors: P
authors: Amero
authors: Department of Pharmacy, Federico II University of Naples, Via Montesano 49, 80131 Naples, Italy.
authors: Anna
authors: A
authors: Santoro
authors: Department of Veterinary Medicine and Animal Productions, Federico II University of Naples, Via Delpino 1, 80137 Naples, Italy.
authors: Anna
authors: A
authors: Monnolo
authors: Department of Pharmacy, Federico II University of Naples, Via Montesano 49, 80131 Naples, Italy.
authors: Raffaele
authors: R
authors: Simeoli
authors: Department of Pharmacy, Federico II University of Naples, Via Montesano 49, 80131 Naples, Italy.
authors: Francesca
authors: F
authors: Di Guida
authors: Department of Pharmacy, Federico II University of Naples, Via Montesano 49, 80131 Naples, Italy. Electronic address: mattace@unina.it.
authors: Giuseppina
authors: G
authors: Mattace Raso
authors: Department of Pharmacy, Federico II University of Naples, Via Montesano 49, 80131 Naples, Italy. Electronic address: meli@unina.it.
authors: Rosaria
authors: R
authors: Meli
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects*; D000818:Animals; D001391:Azo Compounds; D015153:Blotting, Western; D002454:Cell Differentiation; D004396:Coloring Agents; D004785:Environmental Pollutants / Q000633:toxicity*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D020738:Leptin / Q000502:physiology*; D050356:Lipid Metabolism / Q000187:drug effects*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D054411:Receptors, Leptin / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
chemical_list: D001391:Azo Compounds; D004396:Coloring Agents; D004785:Environmental Pollutants; D015850:Interleukin-6; D020738:Leptin; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; C491411:Socs3 protein, mouse; C494087:Stat3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014409:Tumor Necrosis Factor-alpha; D011078:Polychlorinated Biphenyls; D020928:Mitogen-Activated Protein Kinases; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516609:Ptpn1 protein, mouse; C011049:oil red O
keywords: AMPK/ACC pathway; Leptin receptor; Non-dioxin-like polychlorinated biphenyls; Pro-inflammatory cytokines; Signal transducer and activator of transcription 3