Oxidative stress increases S2P protein. HepG2 cells were incubated with cumene hydroperoxide (CHP, 0.5 μmol/L, grey) overnight. CHP increased 4-HNE adducts (A,B) without changes in viability (C) and increased S2P protein expression (D,E) without changes in mRNA (F). CHP requires high glucose media (25 mmol/L glucose) to induce triglyceride accumulation (I) and increase SREBP-1 nuclear translocation (G,H). Control (n = 9) and NAFLD (n = 9) liver tissue samples were obtained through the Liver Tissue and Cell Distribution System (LTCDS). NAFLD patients had significantly higher protein levels of S2P (J,K) as well as 4-HNE (M) compared to controls without changes in S2P mRNA (L). qPCR data was normalized to 18s. B,I mean ± SEM, n = 2; C, mean ± SD, n = 2; E,F mean ± SEM, n = 3; G mean ± SD, n = 3; K, L, M mean ± SEM, n = 17. Bars not sharing the same letter are significantly different p < 0.05.