1. Lead enhancement of 3T3-L1 fibroblasts differentiation to adipocytes involves ERK, C/EBPβ and PPARγ activation
- Author
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María Magdalena Codesido, Maria del Carmen Vila, Claudia Noemí Martini, Graciela Bonifacino, and Matias Gabrielli
- Subjects
0301 basic medicine ,MAPK/ERK pathway ,medicine.medical_specialty ,Cell signaling ,3T3-L1 FIBROBLASTS ,MAP Kinase Signaling System ,Otras Ciencias Biológicas ,Clinical Biochemistry ,Peroxisome proliferator-activated receptor ,010501 environmental sciences ,Biology ,01 natural sciences ,LEAD ,Ciencias Biológicas ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Downregulation and upregulation ,3T3-L1 Cells ,Internal medicine ,Adipocyte ,Adipocytes ,medicine ,Animals ,Molecular Biology ,0105 earth and related environmental sciences ,chemistry.chemical_classification ,Adipogenesis ,PPARΓ ,CCAAT-Enhancer-Binding Protein-beta ,3T3-L1 ,Cell Biology ,General Medicine ,Fibroblasts ,Cell cycle ,ADIPOGENESIS ,Cell biology ,PPAR gamma ,ERK ,030104 developmental biology ,Endocrinology ,Lead ,chemistry ,CIENCIAS NATURALES Y EXACTAS - Abstract
Lead (Pb) is an environmental and industrial contaminant that still represents a public health problem. Elevated Pb exposure has been inversely correlated with femoral bone density and associated with osteoporosis. In the last years, it has been shown that inhibition of osteogenesis from mesenchymal stem cells activates adipogenesis and vice versa. In this paper, we investigated the effect of Pb on the differentiation of 3T3-L1 fibroblasts to adipocytes which is the cell model most used to study adipogenesis. After induction of differentiation, 2 days post-confluent cells re-enter the cell cycle and undergo mitotic clonal expansion (MCE) followed by expression of genes that produce the adipocyte phenotype. The presence of concentrations of Pb up to 10 μM during differentiation of 3T3-L1 fibroblasts did not interfere with MCE but enhanced the accumulation of cytosolic lipids that occur during adipogenesis, as well as, the induction of PPARγ, the master gene in adipogenesis. It is known that PPARγ upregulation is subsequent to induction of C/EBPβ and ERK activation, which are early events in adipogenesis. We found that both events were enhanced by Pb treatment. Our results support a stimulatory effect of Pb on adipogenesis which involves ERK activation and C/EBPβ upregulation prior to PPARγ and adipogenesis activation. Fil: Martini, Claudia Noemí. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina Fil: Gabrielli, Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina Fil: Bonifacino, Graciela. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina Fil: Codesido, María Magdalena. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina Fil: Vila, Maria del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
- Published
- 2017