Ferentially expressed genes were detected after four hours, one week and twelve weeks of supplementation with either fish oil (FO) or corn oil in normo- and dyslipidemic men using whole genome microarrays. Results: Independent of the oil, a significantly higher number of genes was regulated in dyslipidemic subjects compared to normolipidemic subjects. Pathway analyses discovered metabolisms dominantly affected by FO after twelve weeks of supplementation, including the lipid metabolism, immune system and cardiovascular diseases. Several pro-inflammatory genes, in particular, were down-regulated in dyslipidemic subjects, indicating the immune-modulatory and anti-inflammatory capability of FO and its bioactive FAs, eicosapentaenoic acid and docosahexaenoic acid. Conclusions: PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/744568 This is the first study showing significant differences in gene expression profiles between normo- and dyslipidemic men after FO supplementation. 4-(Thiophen-2-yl)pyridin-3-amine Further studies need to clarify the exact role of n-3 PUFAs in pathways and metabolisms which were identified as being regulated after FO supplementation in this study. Trial registration: ClinicalTrials.gov (ID: NCT01089231) Keywords: Lipid metabolism, Dyslipidemia, Hypertriglyceridemia, Pathway analysis, Cardiovascular disease, Gene regulation, Genome microarrays, Omega-3 fatty acids, Omega-3 indexBackground Numerous epidemiologic and intervention studies have shown the beneficial effects of fish oil (FO) and its principal omega-3 poly unsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3), in the prevention of atherosclerosis and cardiovascular diseases (CVD) [1-3]. EPA and DHA are known to affect PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/3081428 the lipid profile by reducing the elevated triacylglycerol (TG) level s12998-016-0127-6 and increasing the high density lipoprotein (HDL) level [4,5]. Due to the effects on lipid levels, subjects Ethyl 5-bromo-6-chloropicolinate with dyslipidemia, especially* Correspondence: Schuchardt@nutrition.uni-hannover.de Equal contributors 1 Institute of Food Science and Human Nutrition, Leibniz University of Hannover, Am Kleinen Felde 30, 30167, Hannover, Germany Full list of author information is available at the end of the articlehypertriglyceridemia, benefit from FO supplementation to reduce the cardiovascular risk [6-8]. Beyond the positive effects on lipid levels, other cardioprotective effects of EPA and DHA are known involving anti-inflammation, modulation of cardiac ion channels, influence on membrane microdomains and downstream cell signaling pathways, anti-thrombotic and anti-arrhythmic effects, induction of hemodynamic changes, and improvement of endothelial function [9,10]. The underlying molecular mechanisms by which EPA and DHA exert these beneficial effects on cardiovascular health are not completely understood. It is believed that many effects of n-3 PUFAs are mediated by interferences with signaling transduction pathways [11]. N-3 PUFAs are known to affect a myriad of molecular pathways, including the regulation of gene expression?2012 Schmidt et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Schmidt et al. Lipids in Health and Disease 2012, 11:105 http://www.lipidworld.com/content/11/1/Page 2 of[12]. This regulation can be driven by n-3 PUFAs directly, or by.