Journal
PHYSIOLOGICAL GENOMICS
Volume 43, Issue 23, Pages 1307-1318Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/physiolgenomics.00100.2011
Keywords
peroxisome proliferator-activated receptor; liver; lipid metabolism; complement and coagulation cascades
Categories
Funding
- Netherlands Nutrigenomics Centre
- Netherlands Heart Foundation [2006B195]
Ask authors/readers for more resources
Lu Y, Boekschoten MV, Wopereis S, Muller M, Kersten S. 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 downregulated 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-alpha, 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available