A Comparative Study of Mouse Hepatic and Intestinal Gene Expression Profiles under PPARα Knockout by Gene Set Enrichment Analysis

Gene expression profiling of PPARα has been used in several studies, but fewer studies went further to identify the tissue-specific pathways or genes involved in PPARα activation in genome-wide. Here, we employed and applied gene set enrichment analysis to two microarray datasets both PPARα related respectively in mouse liver and intestine. We suggested that the regulatory mechanism of PPARα activation by WY14643 in mouse small intestine is more complicated than in liver due to more involved pathways. Several pathways were cancer-related such as pancreatic cancer and small cell lung cancer, which indicated that PPARα may have an important role in prevention of cancer development. 12 PPARα dependent pathways and 4 PPARα independent pathways were identified highly common in both liver and intestine of mice. Most of them were metabolism related, such as fatty acid metabolism, tryptophan metabolism, pyruvate metabolism with regard to PPARα regulation but gluconeogenesis and propanoate metabolism independent of PPARα regulation. Keratan sulfate biosynthesis, the pathway of regulation of actin cytoskeleton, the pathways associated with prostate cancer and small cell lung cancer were not identified as hepatic PPARα independent but as WY14643 dependent ones in intestinal study. We also provided some novel hepatic tissue-specific marker genes.