Capsaicin and Its Combination with Oleic Acid Affect Membrane Fatty Acid Remodeling and Cytokine–Chemokine Secretion in HepG2 Cells

Capsaicin, the main pungent component of chili peppers, exhibits several bioactive properties, such as modulation of adipogenesis and inhibition of liver steatosis by reducing cytoplasmic lipid accumulation. However, no evidence is currently available regarding its effect on the membrane fatty acid remodeling. In this work, we focused on the HepG2 cell model, commonly employed for hepatotoxicity, to examine the lipidome changes after treatment with capsaicin (10 µM), and its combination with oleic acid (100 µM), following the effects after 1.5, 3, and 24 h. In addition, cell viability, lipid accumulation, and secretion of inflammatory mediators were assessed. Notably, the combination of capsaicin with oleic acid completely reverted the correlation between cytokine/chemokine levels and omega-6/omega-3 fatty acids compared to capsaicin alone. Additionally, the combined treatment influenced the protective effect of capsaicin against polyunsaturated fatty acids, as investigated through biomimetic experiments.