Persistent elevation of paraoxonase-1 specific enzyme activity after weight reduction in obese non-diabetic men with metabolic syndrome.

Background: Paraoxonase-1 (PON1) is an esterase associated with the high-density lipoprotein (HDL) in serum. To date, there have been few reports about circulating PON1 protein concentration and specific activity in subjects with metabolic syndrome (MetS). More importantly, it is unknown whether weight loss could alter PON1 protein expression or specific activity in obese non-diabetic men with MetS.

Methods: We prospectively enrolled a total of 40 obese non-diabetic men with MetS. Among them, 22 subjects finished the 3-month course of weight loss program and complied for longer follow-ups post-weight loss at the 3rd, 12th, and 18th month from the beginning of the program. Twenty-six healthy volunteers served as controls. Serum circulating PON1 concentration was measured by an enzyme linked immunosorbent kit (ELISA) and PON1 activity was measured by an automated PON1 activity assay.

Results: Obese non-diabetic men with MetS (n=40) had a higher PON1 protein concentration (31.0 ± 11.3 vs. 24.8 ± 9.7 μg/ml, p=0.025) but lower specific enzyme activity (7.5 ± 4.0 vs. 11.2 ± 7.2 mU/μg, p=0.023) than those of the controls. Multivariate regression analysis of baseline PON1 specific activity revealed that adiponectin was a significant positive predictor (p=0.044) while monocyte chemotactic protein-1 (MCP-1) was a negative predictor (p=0.031). After a 3-month weight loss program, obese MetS men (n=22) had a significant weight reduction (95.8 ± 9.0 to 86.3 ± 10.4 kg, with a 9.9 ± 5.4% decrease, p<0.001). PON1 protein decreased significantly after weight loss and kept declining through the 3rd month till the 18th month follow-up. PON1 specific enzyme activity (baseline 7.5 ± 2.6 mU/μg) increased significantly after weight loss and kept increasing through the 12th month till the 18th month follow-ups (11.8 ± 6.4 mU/μg, p=0.001 vs. baseline).

Conclusions: Weight loss by a 3-month diet and exercise program time-sequentially increased PON1 specific enzyme activity in obese non-diabetic men with MetS.