Email updates

Keep up to date with the latest news and content from BMC Genomics and BioMed Central.

Open Access Research article

Filling gaps in PPAR-alpha signaling through comparative nutrigenomics analysis

Duccio Cavalieri1*, Enrica Calura1, Chiara Romualdi2, Emmanuela Marchi1, Marijana Radonjic34, Ben Van Ommen34 and Michael Müller45

Author Affiliations

1 Department of Pharmacology, University of Firenze, Firenze, Italy

2 Department of Biology, University of Padova, Padova, Italy

3 TNO Quality of Life, BU Biosciences, the Netherlands

4 Nutrigenomics Consortium, Top Institute Food and Nutrition, Wageningen, the Netherlands

5 Division of Human Nutrition, Nutrition, Metabolism and Genomics group, Wageningen University, the Netherlands

For all author emails, please log on.

BMC Genomics 2009, 10:596  doi:10.1186/1471-2164-10-596

Published: 11 December 2009

Abstract

Background

The application of high-throughput genomic tools in nutrition research is a widespread practice. However, it is becoming increasingly clear that the outcome of individual expression studies is insufficient for the comprehensive understanding of such a complex field. Currently, the availability of the large amounts of expression data in public repositories has opened up new challenges on microarray data analyses. We have focused on PPARα, a ligand-activated transcription factor functioning as fatty acid sensor controlling the gene expression regulation of a large set of genes in various metabolic organs such as liver, small intestine or heart. The function of PPARα is strictly connected to the function of its target genes and, although many of these have already been identified, major elements of its physiological function remain to be uncovered. To further investigate the function of PPARα, we have applied a cross-species meta-analysis approach to integrate sixteen microarray datasets studying high fat diet and PPARα signal perturbations in different organisms.

Results

We identified 164 genes (MDEGs) that were differentially expressed in a constant way in response to a high fat diet or to perturbations in PPARs signalling. In particular, we found five genes in yeast which were highly conserved and homologous of PPARα targets in mammals, potential candidates to be used as models for the equivalent mammalian genes. Moreover, a screening of the MDEGs for all known transcription factor binding sites and the comparison with a human genome-wide screening of Peroxisome Proliferating Response Elements (PPRE), enabled us to identify, 20 new potential candidate genes that show, both binding site, both change in expression in the condition studied. Lastly, we found a non random localization of the differentially expressed genes in the genome.

Conclusion

The results presented are potentially of great interest to resume the currently available expression data, exploiting the power of in silico analysis filtered by evolutionary conservation. The analysis enabled us to indicate potential gene candidates that could fill in the gaps with regards to the signalling of PPARα and, moreover, the non-random localization of the differentially expressed genes in the genome, suggest that epigenetic mechanisms are of importance in the regulation of the transcription operated by PPARα.