Long-term weight loss decreases the nontraditional cardiovascular risk factors interleukin-18 and matrix metalloproteinase–9 in obese subjects

The objective of the study was to investigate the effect of long-term (3.2 years) weight loss on serum levels of the nontraditional cardiovascular risk factors interleukin (IL)-18 and matrix metalloproteinase (MMP)–9. Moreover, we wanted to assess the significance of the magnitude of the weight loss and evaluate the potential effects of 36 months of treatment with the lipase inhibitor orlistat on these parameters. Sixty-eight abdominally obese subjects completed 8 weeks of very low energy diet (600-800 kcal/d) followed by 36 months of randomized treatment with either orlistat or placebo together with lifestyle intervention. Serum levels of IL-18, MMP-9, and leptin were measured by flowmetric xMAP technology (Luminex, Austin, TX). Changes in the levels of IL-18, MMP-9, and leptin were similar in the orlistat and the placebo group during this study. Thus, the 2 groups were combined for further analysis. A weight loss of 8.4 ± 8.8 kg from baseline to 3.2 years was associated with significant decreases in IL-18 (P < .001), MMP-9 (P < .01), and leptin (P < .001). Matrix metalloproteinase–9 was, however, significantly increased after 8 weeks of very low energy diet–induced weight loss (P < .05). The long-term changes in IL-18 were significantly associated with changes in body mass index independent of changes in blood pressure and lipids (P < .05). Levels and changes of IL-18 and MMP-9 were significantly positively associated at 3.2 years (P < .01). Long-term changes in leptin were significantly associated with changes in IL-18 (P < .01) at 3.2 years. Diet-induced long-term weight loss decreased IL-18 and MMP-9. The decrease in IL-18 was associated with changes in body mass index independent of changes in blood pressure and lipids, indicating that even a minor weight reduction (>5%) has beneficial effects on nontraditional cardiovascular risk markers. Orlistat treatment had no independent effects on IL-18, MMP-9, or leptin in the present study.