Date of Award
Doctor of Philosophy (PhD)
Humans are continuously exposed to mixtures of environmental pollutants. Polycyclic aromatic hydrocarbons (PAHs), such as 2-naphthol, and heavy metals, such as lead, are some of these pollutants. Results from epidemiological studies show associations between exposure to 2-naphthol, exposure to lead, and obesity. However, the individual and combined effects of 2-naphthol and lead on fat cell development (adipogenesis) have not been directly characterized in a biological system. In this study, we evaluated the effects of 2-naphthol and/or lead on adipogenesis using mouse 3T3-L1 cells.
Cells were exposed to different doses of 2-naphthol and/or lead. Induced terminal differentiation was evaluated by cell morphology, lipid production, and mRNA expression of marker genes characteristic of either early adipocyte differentiation: CCAAT-enhancer-binding protein β (C/EBPβ), insulin receptor substrate 2 (IRS2), and sterol responsive element binding protein 1 c (SREBP1c); or terminal differentiation: C/EBPα, peroxisome proliferator-activated receptor-γ (PPARγ), and fatty acid binding protein 4 (aP2). Production of antimicrobial peptide cathelicidin (Camp), which is produced by differentiating adipocytes and modulates inflammation and immunity, was also evaluated.
Cell morphology changes and increased lipid accumulation indicated that, individually, 2-naphthol and lead induced 3T3-L1 differentiation; however, the highest dose of lead (10 μM) showed the lowest induction level. During terminal differentiation, 2-naphthol and low doses of lead increased C/EBPα, PPARγ, and aP2 expression, whereas 10 μM lead suppressed PPARγ and aP2. During early differentiation, 2-naphthol stimulated C/EBPβ, IRS2, and SREBP1c expression, while lead upregulated C/EBPα and aP2. The 2-naphthol/10 μM lead mixture induced a counterbalancing effect on 3T3-L1 adipogenesis, where 10 μM lead suppressed 2-naphthol-induced adipogenesis. Moreover, 2-naphthol elevated Camp expression in a dose-dependent manner, whereas lead slightly increased Camp at lower doses but suppressed it at 10 μM. The 2-naphthol/10 μM lead mixture showed no effect on Camp expression.
In conclusion, 2-naphthol and low lead doses accelerate adipocyte differentiation and Camp production in 3T3-L1 cells; however, high doses of lead attenuate the induction. This effect of lead at high dose counterbalances the upregulation of adipocyte differentiation and Camp production by 2-naphthol. Together, these findings indicate that 2-naphthol and lead play potential roles in the development of inflammation and obesity.
Wang, Jing, "The Effects Of Environmental Pollutants On Adipogenesis In The 3T3-L1 Model." Dissertation, Georgia State University, 2015.