Sulfo‐N‐Succinimidyl Oleate Sodium as CD36 Inhibitor: Dose Optimization and Its Effects on FFA Uptake, Inflammation, and ER Stress in HepG2 Cells

The risk of metabolic disorders is increasing due to high-fat diets. An imbalance between the absorption and utilization of fatty acids results in lipid accumulation. CD36 is a scavenger receptor involved in fatty acid uptake and immunity. Theoretically, CD36 inhibition will prevent lipid accumulation. CD36 has several known inhibitors, such as sulfo-N-succinimidyl oleate sodium (SSO). Therefore, this study aimed to find the optimal concentration of SSO on HepG2 cells and its effects on FFA uptake, ER stress, and inflammation. HepG2 cell viability assay against various concentrations of SSO was conducted to determine the 50% cell growth inhibition (IC50). The cultures were given SSO in IC50, ½ IC50, ¼ IC50, and 1/8 IC50 concentrations and treated with palmitic acid. Cell morphology was observed. FFA uptake was evaluated. Real-time PCR was used to determine CHOP, IL-8, and TNFα mRNA expressions. The ¼ IC50 of SSO is effective in inhibiting FFA uptake without causing a decrease in cell viability. Downregulation of CHOP, IL-8, and TNFα was seen after SSO administration, especially at ¼ IC50. In conclusion, the ¼ IC50 SSO concentration was the safest and most optimal concentration in reducing FFA uptake and the expressions of IL-8, TNFα, and CHOP in HepG2 cells.