DINCH and DINP Plasticizers Alter Lipid Metabolism in 3T3-L1 cells
2022
Häggblom, Isabel
Di(isononyl)cyclohexane – 1,2 dicarboxylate (DINCH) and Diisononyl phthalate (DINP) are high molecular weight compounds used as plasticizers. DINCH and DINP use on the market have been increasing recently to replace previously used phthalate plasticizers in polymeric products. Exposure to the compounds DINCH and DINP has been shown to be targeting the adipose tissue and potentially inducing lipid metabolism. However, few studies have reported the potential toxicity of these plasticizers and in this study, their effect on the 3T3-L1 cell line was investigated. The preadipocytes 3T3-L1 cell lines were exposed to 1 μM, 10 μM, and 100 μM DINCH and DINP for 10 days and assessed by lipid accumulation, gene expression, and protein analysis. The result of the lipid accumulation showed that higher concentrations of DINCH and DINP can induce adipogenesis. The proliferator-activated receptor gamma (Pparγ) agonist Rosiglitazone (Rosi) was used as a positive control. Further, the result of DINCH and DINP on gene expression showed that these compounds can both upregulate and downregulate genes involved in adipogenesis. The plasticizers DINCH and DINP upregulated proliferator-activated receptor-gamma and alpha (Pparγ, Pparα), CCAAT/enhancer-binding protein alpha (C/EBPα) and the fatty acid-binding protein 4 and 5 (Fabp4, Fabp5) and downregulated Fatty acid synthase (Fasn) and Gata binding factor 2 (Gata2) transcript levels. Protein analysis using Western blot showed that both DINCH and DINP can downregulate FASN protein expression. From this study, it can be concluded that DINCH and DINP influence the metabolic pathways and this can be a serious threat to animals and humans as the use and their levels in the environment are increasing.
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