Nuclear receptors expression chart in peripheral blood mononuclear cells identifies patients with Metabolic Syndrome.
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.


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.
Clinica Medica "A. Murri", "Aldo Moro" University of Bari, Italy; National Cancer Research Center, IRCCS Oncologico Giovanni Paolo II, Bari, Italy; Laboratory of Lipid Metabolism and Cancer, Consorzio Mario Negri Sud, Santa Maria Imbaro (Chieti), Italy.
Simona
S
D'Amore
Michele
M
Vacca
Giusi
G
Graziano
Andria
A
D'Orazio
Marica
M
Cariello
Nicola
N
Martelli
Giuseppe
G
Di Tullio
Roberto
R
Salvia
Giuseppe
G
Grandaliano
Anna
A
Belfiore
Fabio
F
Pellegrini
Giuseppe
G
Palasciano
Antonio
A
Moschetta
D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D016022:Case-Control Studies; D015331:Cohort Studies; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D024821:Metabolic Syndrome / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D015415:Biomarkers; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors
Epidemiology; Gene expression; Inflammation; Metabolic Syndrome; Nuclear receptors