Abstract
Current evidence indicates that chemical pollutants may interfere with the homeostatic control of nutrient metabolism, thereby contributing to the increased prevalence of metabolic disorders. Bisphenol-A (BPA) is a lipophilic compound contained in plastic which is considered a candidate for impairing energy and glucose metabolism. We have investigated the impact of low doses of BPA on adipocyte metabolic functions. Human adipocytes derived from subcutaneous adipose tissue and differentiated 3T3-L1 cells were incubated with BPA, in order to evaluate the effect on glucose utilization, insulin sensitivity and cytokine secretion. Treatment with 1 nM BPA significantly inhibited insulin-stimulated glucose utilization, without grossly interfering with adipocyte differentiation. Accordingly, mRNA levels of the adipogenic markers PPARγ and GLUT4 were unchanged upon BPA exposure. BPA treatment also impaired insulin-activated receptor phosphorylation and signaling. Moreover, adipocyte incubation with BPA was accompanied by increased release of IL-6 and IFN-γ, as assessed by multiplex ELISA assays, and by activation of JNK, STAT3 and NFkB pathways. Treatment of the cells with the JNK inhibitor SP600125 almost fully reverted BPA effect on insulin signaling and glucose utilization. In conclusion, low doses of BPA interfere with inflammatory/insulin signaling pathways, leading to impairment of adipose cell function.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3-L1 Cells
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Adipocytes / drug effects
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Adipocytes / metabolism*
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Adipocytes / pathology*
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Animals
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Benzhydryl Compounds / pharmacology*
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Cell Differentiation / drug effects
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Cell Differentiation / genetics
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Down-Regulation / drug effects
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Glucose / metabolism
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Humans
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Inflammation / genetics
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Inflammation / pathology*
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Insulin / pharmacology*
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JNK Mitogen-Activated Protein Kinases / metabolism
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Leptin / genetics
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Leptin / metabolism
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Mice
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NF-kappa B / metabolism
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Phenols / pharmacology*
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Phosphorylation / drug effects
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptor, Insulin / genetics
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Receptor, Insulin / metabolism
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STAT3 Transcription Factor / metabolism
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Signal Transduction / drug effects
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Signal Transduction / genetics
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Subcutaneous Fat / pathology*
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Up-Regulation / drug effects*
Substances
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Benzhydryl Compounds
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Insulin
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Leptin
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NF-kappa B
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Phenols
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RNA, Messenger
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STAT3 Transcription Factor
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Receptor, Insulin
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JNK Mitogen-Activated Protein Kinases
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Glucose
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bisphenol A
Grants and funding
The manuscript was supported in part by EC FP6 PREPOBEDIA (201681); Associazione Italiana per la Ricerca sul Cancro - AIRC (IG 12136); European Foundation for the Study of Diabetes (EFSD Diabetes and Cancer Programme 2011); MIUR - PRIN (prot.2010MCLBCZ_003); MIUR - FIRB MERIT (RBNE08NKH7_011). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.