SERPINE1, PAI-1 protein coding gene, methylation levels and epigenetic relationships with adiposity changes in obese subjects with metabolic syndrome features under dietary restriction

Patricia Lopez-Legarrea, Maria Luisa Mansego, Marian Angeles Zulet, Jose Alfredo Martinez, Patricia Lopez-Legarrea, Maria Luisa Mansego, Marian Angeles Zulet, Jose Alfredo Martinez

Abstract

Plasminogen activator inhibitor 1 (PAI-1) has been associated with metabolic disorders, through different mechanisms, which could involve changes in DNA methylation. This work aimed to assess the potential relationships of the cytosine methylation levels within SERPINE1 gene transcriptional regulatory region, which codes for PAI-1, in peripheral white blood cells with anthropometrical, metabolic and inflammatory features. Forty-six obese subjects with metabolic syndrome features followed Control or Metabolic Syndrome Reduction in Navarra (RESMENA) energy-restricted (-30%E) diets for 8 weeks. SERPINE1 transcriptional regulatory region methylation at baseline was analyzed by a microarray technical. Both dietary strategies reduced anthropometric and biochemical parameters. The Control group significantly reduced plasma PAI-1 concentrations but not the RESMENA group. Participants from both nutritional interventions with higher SERPINE1 methylation levels at baseline showed significantly major reductions in body weight, total fat mass, android fat mass, total cholesterol and triglycerides, as compared with those with lower initial SERPINE1 methylation levels. In conclusion, the DNA methylation levels of SERPINE1 transcriptional regulatory region were associated with some metabolic and anthropometric changes in obese subjects with metabolic syndrome under energy restriction, suggesting a complex epigenetic network in the regulation of this recognized pro-inflammatory marker. (www.clinicaltrials.gov; NCT01087086).

Keywords: DNA methylation; PAI-1; SERPINE1 gene; energy restriction; metabolic syndrome.

Figures

Fig. 1
Fig. 1
Genomic localization and nucleotide sequence of 10 CpGs sites covered by the Illumina probe for the study of DNA methylation levels of plasminogen activator inhibitor type 1 promoter (from −1408 to +113 bp). Transcription Start Site (TSS). CpG 10 has a putative consensus sequences for (E2F-1), found with MatInspector.
Fig. 2
Fig. 2
Changes in PAI-1 plasma concentrations in Control and RESMENA groups from baseline to the endpoint of the intervention and differences between them (A); comparison between Control and RESMENA groups levels of SERPINE1 CpG 10 methylation (%) at baseline (B); comparison of PAI-1 plasma concentrations within Control and RESMENA groups according to SERPINE1 CpG 10 baseline methylation level (%) (C) and correlation analysis between methylation in the SERPINE1 CpG 10 and total fat mass by Dual-energy X-ray absorptiometry at baseline (D). PAI-1: plasminogen activator inhibitor 1.

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