Transcriptomics

Dataset Information

10

Comparative transcriptomics and metabolomic analysis of fenofibrate and fish oil treatments in mice


ABSTRACT: 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 week treatment withfenofibrate and fish oil in mice. Plasma triglycerides were significantly decreased byfenofibrate (-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 PPARα, 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 towards 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. Expression profiling of liver from mice fed control diet, fish oil or fenofibrate for 2 weeks.

REANALYSED by: E-GEOD-32706

ORGANISM(S): Mus musculus  

SUBMITTER: Suzan Wopereis   Mark V Boekschoten  Sander Kersten  Michael Müller  Yingchang Lu  Guido Hooiveld 

PROVIDER: E-GEOD-32706 | ArrayExpress | 2011-10-07

SECONDARY ACCESSION(S): GSE32706PRJNA147003

REPOSITORIES: GEO, ArrayExpress

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Publications

Comparative transcriptomic and metabolomic analysis of fenofibrate and fish oil treatments in mice.

Lu Yingchang Y   Boekschoten Mark V MV   Wopereis Suzan S   Müller Michael M   Kersten Sander S  

Physiological genomics 20110927 23


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 (+2  ...[more]

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