Oleic acid promotes adaptability against oxidative stress in 3T3-L1 cells through lipohormesis

Although fatty acids are important components of biological membranes, energy sources, and signal transducers or precursors of lipid mediators, excess intake of fatty acids and their accumulation cause obesity and metabolic syndrome. Thus, fatty acid quantity is known to be an important factor for obesity-related diseases, but the effects of different types of fatty acids (i.e., fatty acid quality) on human health are not completely understood. We here focused on the relationship between fatty acid quality and oxidative stress by investigating whether resistibility to tert-butyl hydrperoxide (t-BuOOH)-induced oxidative stress in 3T3-L1 cells varied according to the fatty acid type. Among eight fatty acids (both saturated and unsaturated) tested, oleic acid (OA) exerted the most pronounced cytoprotective effects, with efficacy over a wide range of concentrations. OA treatment markedly enhanced the intracellular levels of lipid peroxidation markers, including N(ε)-(hexanoyl)lysine, 4-hydroxy-2-nonenal, and acrolein. The levels of these markers in OA-treated cells were decreased after t-BuOOH exposure, whereas the levels in untreated control cells were notably increased after t-BuOOH exposure. Our results suggested that unsaturated fatty acids, particularly OA, could promote an adaptive response and enhance cell tolerance through increased cellular antioxidative capacity via OA-induced mild lipid peroxidation (lipohormesis), and thus protect cells against subsequent oxidative stress-related injury.