BackgroundWater-soluble phenolics from the oil palm possess significant biological properties.PurposeIn this study, we aimed to discover the role of oil palm phenolics (OPP) in influencing the gene expression changes caused by an atherogenic diet in mice.MethodsWe fed mice with either a low-fat normal diet (14.6 % kcal/kcal fat) with distilled water, or a high-fat atherogenic diet (40.5 % kcal/kcal fat) containing cholesterol. The latter group was given either distilled water or OPP. We harvested major organs such as livers, spleens and hearts for microarray gene expression profiling analysis. We determined how OPP changed the gene expression profiles caused by the atherogenic diet. In addition to gene expression studies, we carried out physiological observations, blood hematology as well as clinical biochemistry, cytokine profiling and antioxidant assays on their blood sera.ResultsUsing Illumina microarrays, we found that the atherogenic diet caused oxidative stress, inflammation and increased turnover of metabolites and cells in the liver, spleen and heart. In contrast, OPP showed signs of attenuating these effects. The extract increased unfolded protein response in the liver, attenuated antigen presentation and processing in the spleen and up-regulated antioxidant genes in the heart. Real-time quantitative reverse transcription-polymerase chain reaction validated the microarray gene expression fold changes observed. Serum cytokine profiling showed that OPP attenuated inflammation by modulating the Th1/Th2 axis toward the latter. OPP also increased serum antioxidant activity to normal levels.ConclusionThis study suggests that OPP may possibly attenuate atherosclerosis and other forms of cardiovascular disease.Electronic supplementary materialThe online version of this article (doi:10.1007/s00394-012-0346-0) contains supplementary material, which is available to authorized users.