Nuclear receptors (NRs) control metabolism/inflammation in lympho-monocyte (PBMC).
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Metabolic Syndrome (MS) is characterized by changes of NR transcriptome in PBMCs.
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NOR1 and PPARδ expression is reduced in PBMCs of patients with MS.
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NOR1 and PPARδ expression correlates with lipid metabolism and inflammation markers.
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NOR1 and PPARδ transcripts in PBMCs are promising biomarkers in MS.
Abstract
Background
Nuclear receptors are a class of 48 ligand-activated transcription factors identified as key players of metabolic and developmental processes. Most of these receptors are potential targets for pharmacological strategies in the Metabolic Syndrome. In the present study, we analyzed changes in the mRNA expression of nuclear receptors in the peripheral blood mononuclear cells of patients with Metabolic Syndrome, in order to identify novel biomarkers of disease and candidate targets for putative therapeutical approaches.
Methods and results
We enrolled thirty healthy controls (14 M:16 F) and thirty naïve patients (16 M: 14 F; > 3 criteria for Metabolic Syndrome upon Adult Treatment Panel III) without organ damage. Using quantitative real-time PCR, we assessed the expression patterns of nuclear receptors in peripheral blood mononuclear cells. 33/48 nuclear receptors were expressed in peripheral blood mononuclear cells. In patients with Metabolic Syndrome, we found a significant down-regulation of the entire PPAR, NR4A and RAR families, together with a repression of RXRα, VDR, and Rev-Erbα. Furthermore, we performed a novel statistical analysis with classification trees, which allowed us to depict a predictive core of nuclear receptor expression patterns characterizing subjects with Metabolic Syndrome. Random Forest Analysis identified NOR1 and PPARδ, which were both reduced in peripheral blood mononuclear cells and specifically in CD14+ cells (mostly monocytes), as classifiers of Metabolic Syndrome, with high specificity and sensitivity.
Conclusions
Our results point to the use of PPAR and NR4A mRNA levels in the overall peripheral blood mononuclear cells as biomarkers of Metabolic Syndrome and bona fide putative targets of pharmacological therapy.
