Activation of peroxisome proliferator-activated receptor alpha in human peripheral blood mononuclear cells reveals an individual gene expression profile response.
BACKGROUND
Peripheral blood mononuclear cells (PBMCs) are relatively easily obtainable cells in humans. Gene expression profiles of PBMCs have been shown to reflect the pathological and physiological state of a person. Recently, we showed that the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha) has a functional role in human PBMCs during fasting. However, the extent of the role of PPARalpha in human PBMCs remains unclear. In this study, we therefore performed gene expression profiling of PBMCs incubated with the specific PPARalpha ligand WY14,643.


RESULTS
Incubation of PBMCs with WY14,643 for 12 hours resulted in a differential expression of 1,373 of the 13,080 genes expressed in the PBMCs. Gene expression profiles showed a clear individual response to PPARalpha activation between six healthy human blood donors. Pathway analysis showed that genes in fatty acid metabolism, primarily in beta-oxidation were up-regulated upon activation of PPARalpha with WY14,643, and genes in several amino acid metabolism pathways were down-regulated.


CONCLUSIONS
This study shows that PPARalpha in human PBMCs regulates fatty acid and amino acid metabolism. In addition, PBMC gene expression profiles show individual responses to WY14,643 activation. We showed that PBMCs are a suitable model to study changes in PPARalpha activation in healthy humans.
Bouwens
Mark
M
Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Bomenweg 2, 6703 HD Wageningen, The Netherlands. mark.bouwens@wur.nl
Afman
Lydia A
LA
Müller
Michael
M
D000596:Amino Acids / Q000378:metabolism; D005215:Fasting / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D015894:Genome, Human; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D047493:PPAR alpha / Q000819:agonists / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology; D020218:Response Elements
D000596:Amino Acids; D005227:Fatty Acids; D000960:Hypolipidemic Agents; D047493:PPAR alpha; D011743:Pyrimidines; C006253:pirinixic acid