Low-level perfluorooctanoic acid enhances 3 T3-L1 preadipocyte differentiation via altering peroxisome proliferator activated receptor gamma expression and its promoter DNA methylation
Abstract
Recent studies suggest that perfluorooctanoic acid (PFOA) can play a role in the development of obesity; however, the associated mechanisms are poorly understood. We investigated how PFOA exposure affected the differentiation of 3 T3-L1 preadipocytes and the associated transcriptional and epigenetic mechanisms. Cells treated with different doses of PFOA (ranging from 0.01 to 100 μg ml-1 ) were assessed for proliferation, differentiation and triglyceride accumulation. The gene expression levels of peroxisome proliferator activated receptor gamma (PPARγ) and its target genes were measured. DNA methylation levels of PPARγ promoter and global DNA methylation levels were also tested. We found a concentration-dependent enhancement of adipocyte proliferation and differentiation following PFOA exposure. PFOA also induced a significant concentration-dependent increase in the accumulation of lipid and triglyceride. Increased gene expression was also observed for PPARγ, CCAAT/enhancer binding proteins α, fatty acid binding protein 2 and lipoprotein lipase in differentiated cells after PFOA exposure. The ability of PFOA to induce adipogenesis was blocked by GW9662, a known PPARγ antagonist. In addition, significant demethylation of the cyt...Continue Reading
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