Fasting induces changes in peripheral blood mononuclear cell gene expression profiles related to increases in fatty acid beta-oxidation: functional role of peroxisome proliferator activated receptor alpha in human peripheral blood mononuclear cells.

摘要

BACKGROUND: Peripheral blood mononuclear cells (PBMCs) are the only readily available cells in healthy humans. Various studies showed disease-characteristic gene expression patterns in PBMCs. However, little is known of nutritional effects on PBMC gene expression patterns. Fatty acids are nutrients that regulate gene expression by activating the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha). PBMCs express PPARalpha, making these cells interesting to study FA-dependent gene expression. OBJECTIVE: The aim of this study was to elucidate whether PBMC gene expression profiles also reflect nutrition-related metabolic changes. Furthermore, we focused on the specific role of PPARalpha in regulation of PBMC gene expression during fasting, when plasma free fatty acids are elevated. DESIGN: Four healthy male volunteers fasted for 48 h. PBMC RNA was hybridized on Affymetrix whole genome microarrays. To elucidate the role of PPARalpha, PBMCs of 9 blood donors were incubated with the specific PPARalpha ligand Wy14643. RESULTS: After 24 and 48 h of fasting, 1200 and 1386 genes were changed >1.4-fold, respectively. Many of those genes were involved in fatty acid beta-oxidation and are known PPARalpha target genes. Incubation of PBMCs with Wy14643 resulted in up-regulation of genes that were also up-regulated during fasting. CONCLUSIONS: We conclude that PBMC gene expression profiles reflect nutrition-related metabolic changes such as fasting and that part of the fasting-induced changes are likely regulated by PPARalpha.