Adipose tissue is not an important source for matrix metalloproteinase-9 in the circulation

Objectives: Matrix metalloproteinase 9 (MMP-9) is overexpressed in atherosclerotic plaques and in many cancers, and has emerged as a potential circulating biomarker for such diseases. However, adipose tissue (AT) might also produce circulating MMP-9, thereby reducing the value of MMP-9 as a biomarker. The aim of this study was to evaluate the impact of AT on circulating MMP-9, and if the metabolic syndrome might have a modifying effect. Methods: Gene expression of MMP-9 was measured in AT, isolated adipocytes, atherosclerotic plaques, macrophages and various other human tissues using real-time PCR. Relationships between plasma MMP-9 (ELISA), adiposity, and metabolic syndrome were analyzed in a population-based cohort of 61-year-old men (n=513). Both AT mRNA levels and circulating levels of MMP-9 were measured in obese subjects (n=40) with and without the metabolic syndrome, treated with a weight-reducing diet. Results: Bone marrow, atherosclerotic plaques and macrophages had considerably higher MMP-9 mRNA than subcutaneous AT and isolated adipocytes. Among the 61-year-old men, active plasma MMP-9 concentrations were associated with several metabolic syndrome factors, and inflammatory markers, but not body mass index (BMI). In obese patients with, but not without metabolic syndrome AT mRNA levels and circulating MMP-9 declined during weight reduction, but there was no association between changes in plasma MMP-9 and BMI. Conclusion: The results show that adipose tissue per se is not associated with circulating MMP-9. Components of the metabolic syndrome, such as circulating insulin and glucose were related to plasma MMP-9 both in the observation and dietary weight loss studies.