Lead enhancement of 3T3-L1 fibroblasts differentiation to adipocytes involves ERK, C/EBPβ and PPARγ activation

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.

Adipogenesis Regulation and Endocrine Disruptors: Emerging Insights in Obesity

“…is process was further characterized by an inhibition of the cellular signaling pathway of Wnt/β-catenin. More recently, the proadipogenic effect of lead was demonstrated in 3T3-L1 cultures, which involved the activation of the ERK, C/EBPβ, and PPARc pathways [86].…”

Nonylphenol Promotes the Differentiation of 3T3-L1 Preadipocytes

“…This may be the mechanism by which NP causes the onset of type II DM and NAFLD. Results of the measurement of lipid metabolism-related protein levels revealed that NP exposure promoted the expression of the lipid-metabolism-related proteins C/EBPα, FAS, PPARγ, and SREBP1 in 3T3-L1 preadipocytes [32,33]. These proteins play key roles in the proliferation, differentiation, maturation, and lipid metabolism of adipocytes [34].…”

The Antiobesity Effects of Buginawa in 3T3-L1 Preadipocytes and in a Mouse Model of High-Fat Diet-Induced Obesity

“…During this process, the expression of adipogenic transcription factors, including PPAR γ , C/EBP α , and SREBP1 is stimulated [35]. C/EBP β is expressed earlier during adipogenesis because it is required for the induction of MCE caused by MDI medium [36] and then triggers the expression of PPAR γ and C/EBP α in 3T3-L1 cells [37]. The data showed that Bugi markedly suppressed the PPAR γ , C/EBP α , and SREBP1 expression on Day 4 but also C/EBP β expression on Day 2 in differentiated 3T3-L1 cells (Figures 1(e) and 1(f)).…”