Effects of Four Synthetic Phenolic Antioxidants on Adipogenic Differentiation and Potential Mechanisms
Synthetic phenolic antioxidants (SPAs) are widely used, leading to environmental contamination and human exposure. However, studies on their effects on adipocyte differentiation and underlying mechanisms, particularly for emerging SPAs, are limited. This study evaluated the impacts of 4-tert-octylphenol (4-t-OP) and three novel antioxidants (AO 3114, AO 1135, AO 702) on adipogenesis using the mouse 3T3-L1 preadipocyte differentiation model. Lipid staining, triglyceride measurement, differentiation-related gene expression analysis, and transcriptomic approaches were employed. All four SPAs significantly promoted differentiation of 3T3-L1 cells into mature adipocytes and upregulated expression of peroxisome proliferator-activated receptor gamma (Pparγ) and mature adipocyte marker genes. Transcriptomic analysis revealed differential effects on gene transcription during early differentiation. GO and KEGG enrichment analyses indicated that these SPAs promoted adipogenesis by enhancing energy metabolism and protein synthesis, as well as regulating PPAR and other signaling pathways. In conclusion, the tested SPAs promote adipogenesis and disrupt lipid metabolism through distinct mechanisms, suggesting long-term exposure may cause metabolic disorder risks and pose a public health threat.