Curcumin Opposes Perfluorodecanoic Acid-Induced Adipogenesis Through the PPARγ/C/EBPα Axis in 3T3-L1 Cells.

(1) Background: Perfluorodecanoic acid (PFDA), a persistent perfluoroalkyl obesogen, promotes adipogenesis, yet whether its effects can be pharmacologically opposed remains unknown. (2) Methods: We examined the interaction between PFDA (50, 75 μM) and the dietary polyphenol curcumin (20, 30 μM) throughout the 8-day 3T3-L1 preadipocyte differentiation protocol, using cell-viability (WST-1) assays with a two-factor interaction analysis, Oil Red O lipid quantification and mRNA profiling of Pparg, Cebpa, Srebf1, and Fasn. (3) Results: PFDA alone increased lipid accumulation and upregulated Pparg, Cebpa, and Fasn, whereas Srebf1 was induced only weakly and only at the higher dose, a pattern compatible with preferential engagement of the PPARγ/C/EBPα program over the SREBP-1c lipogenic pathway at the mRNA level, although the transcripts were not formally compared and no protein-level data were obtained. At two sub-cytotoxic concentrations, curcumin preserved potent antiadipogenic activity, reducing lipid accumulation by up to 67.3% and reversing PFDA-induced gene upregulation. At the viability endpoint the two compounds acted independently: curcumin significantly reduced viability and PFDA significantly increased it, with no statistically detectable interaction between them (two-way ANOVA, interaction p = 0.85). (4) Conclusions: This dissociation shows that a chemical interaction defined at one biological endpoint does not predict its outcome at another, a principle with broad implications for mixture toxicology-and it establishes curcumin as a candidate dietary intervention that intercepts an obesogen's transcriptional program against environmentally driven metabolic disruption.