Arylesterase activity is associated with antioxidant intake and paraoxonase-1 (PON1) gene methylation in metabolic syndrome patients following an energy restricted diet

Rocio de la Iglesia, Maria L Mansego, Francisco J Sánchez-Muniz, M Angeles Zulet, J Alfredo Martinez, Rocio de la Iglesia, Maria L Mansego, Francisco J Sánchez-Muniz, M Angeles Zulet, J Alfredo Martinez

Abstract

The arylesterase (ARE) activity linked to the paraoxonase-1 (PON1) gene is known to protect lipoproteins from oxidation and provide defense against metabolic syndrome (MetS) and cardiovascular diseases. The epigenetic regulation of enzymatic activities is gaining importance nowadays. This research aimed to assess the potential relationships between the ARE activity with the methylation levels of the PON1 gene transcriptional regulatory region, anthropometrics, biochemical markers and antioxidant dietary components. Forty-seven subjects (47 ± 10 y.o; BMI 36.2 ± 3.8 kg/m(2); 46.8 % female) with MetS features, who followed a six-month energy-restricted dietary weight-loss intervention, were included in this study (www.clinicaltrials.gov; NCT01087086). Anthropometric, biochemical, enzymatic and dietary data were assessed using validated procedures. PON1 transcriptional regulatory region methylation was analyzed by a microarray technical approach. Volunteers reduced ARE activity in parallel with body weight (p = 0.005), BMI (p = 0.006), total fat mass (p = 0.020), diastolic blood pressure (p = 0.018), mean blood pressure (p = 0.022) and triglycerides (p = 0.014). Methylation levels of some CpG sites of the PON1 gene correlated negatively with ARE activity (p < 0.05). Interestingly, dietary vitamin C (p = 0.001), tocopherols (p = 0.009) and lycopene (p = 0.038) were positively associated with ARE activity and showed an inverse correlation (p = 0.004, p = 0.029 and p = 0.021, respectively) with the methylation of some selected CpG sites of the PON1 gene. In conclusion, ARE activity decreased in parallel with MetS-related markers associated to the energy restriction, while dietary antioxidants might enhance the ARE activity by lowering the PON1 gene methylation in patients with MetS features.

Keywords: ARE; DNA methylation; PON1 gene; antioxidants; energy restriction; metabolic syndrome; obesity.

Figures

Table 1. Information of the selected CpG…
Table 1. Information of the selected CpG sites for each PON1 gene
Table 2. Changes in anthropometric, body composition,…
Table 2. Changes in anthropometric, body composition, blood pressure, biochemical parameters and arylesterase (ARE) activity after 6 month-study (N = 47)
Table 3. Pearson correlation analyses between arylesterase…
Table 3. Pearson correlation analyses between arylesterase (ARE) activity variation and changes in selected anthropometric, body composition, blood pressure and biochemical variables.
Table 4. Pearson correlation analyses between arylesterase…
Table 4. Pearson correlation analyses between arylesterase (ARE) activity and the selected CpG sites methylation (%) of PON1 gene at baseline
Figure 1. Genomic localization and nucleotide sequence…
Figure 1. Genomic localization and nucleotide sequence of 8 CpG sites covered by the Illumina probe for the study of DNA methylation levels of PON1 promoter (from - 1330 to +104 pb). Transcription Start Site (TSS).
Figure 2. Associations between antioxidant dietary components…
Figure 2. Associations between antioxidant dietary components intake and arylesterase (ARE) activity
Figure 3. Statistically significant correlations between antioxidant…
Figure 3. Statistically significant correlations between antioxidant dietary components intake and methylation (%) of PON1 gene CpG sites at baseline

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