Print Email Facebook Twitter Comparative transcriptomic and metabolomic analysis of fenofibrate and fish oil treatments in mice Title Comparative transcriptomic and metabolomic analysis of fenofibrate and fish oil treatments in mice Author Lu, Y. Boekschoten, M.V. Wopereis, S. Müller, M. Kersten, S. Publication year 2011 Abstract Comparative transcriptomic and metabolomic analysis of fenofibrate and fish oil treatments in mice. Physiol Genomics 43: 1307-1318, 2011. First published September 27, 2011; doi:10.1152/physiolgenomics.00100.2011. Elevated circulating triglycerides, which are considered a risk factor for cardiovascular disease, can be targeted by treatment with fenofibrate or fish oil. To gain insight into underlying mechanisms, we carried out a comparative transcriptomics and metabolomics analysis of the effect of 2 wk treatment with fenofibrate and fish oil in mice. Plasma triglycerides were significantly decreased by fenofibrate (-49.1%) and fish oil (- 21.8%), whereas plasma cholesterol was increased by fenofibrate (+ 29.9%) and decreased by fish oil (- 32.8%). Levels of various phospholipid species were specifically decreased by fish oil, while levels of Krebs cycle intermediates were increased specifically by fenofibrate. Plasma levels of many amino acids were altered by fenofibrate and to a lesser extent by fish oil. Both fenofibrate and fish oil upregulated genes involved in fatty acid metabolism and down-regulated genes involved in blood coagulation and fibrinolysis. Significant overlap in gene regulation by fenofibrate and fish oil was observed, reflecting their property as high or low affinity agonist for peroxisome proliferator-activated receptor-a, respectively. Fenofibrate specifically downregulated genes involved in complement cascade and inflammatory response. Fish oil specifically downregulated genes involved in cholesterol and fatty acid biosynthesis and upregulated genes involved in amino acid and arachidonic acid metabolism. Taken together, the data indicate that despite being similarly potent toward modulating plasma free fatty acids, cholesterol, and triglyceride levels, fish oil causes modest changes in gene expression likely via activation of multiple mechanistic pathways, whereas fenofibrate causes pronounced gene expression changes via a single pathway, reflecting the key difference between nutritional and pharmacological intervention. © 2011 the American Physiological Society. Subject LifeMSB - Microbiology and Systems BiologyEELS - Earth, Environmental and Life SciencesBiologyHealthy LivingComplement and coagulation cascadesLipid metabolismLiverPeroxisome proliferator-activated receptoramino acidcholesterolfenofibratefish oilperoxisome proliferator activated receptor alphatriacylglycerolamino acid blood levelanimal experimentarachidonic acid metabolismarticlecardiovascular riskcholesterol blood levelcitric acid cyclecomparative studycontrolled studydown regulationfatty acid metabolismfatty acid synthesisgene controlmalemetabolomicsmousenonhumanpriority journaltranscriptomicstreatment durationtriacylglycerol blood levelupregulation To reference this document use: http://resolver.tudelft.nl/uuid:c3ba8684-b042-4b45-acb3-2208cc12b38e DOI https://doi.org/10.1152/physiolgenomics.00100.2011 TNO identifier 445715 ISSN 1094-8341 Source Physiological Genomics, 43 (23), 1307-1318 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.