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Generation of circulating globular adiponectin is catalyzed by thrombin
Author(s) -
Wigle Jeffrey Theodore,
Tworek Leslee,
Taylor Carla G.,
Zahradka Peter
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1093.16
Subject(s) - adiponectin , thrombin , medicine , chemistry , endocrinology , protease , elastase , biochemistry , enzyme , biology , diabetes mellitus , insulin resistance , platelet
The circulating levels of the cardiprotective adipokine adiponectin are reduced in obesity and diabetes. Lower adiponectin levels may contribute to the higher incidence of cardiovascular disease in these conditions. A truncated and biologically active form of adiponectin called globular adiponectin is protective against cardiovascular disease. However, little is known about its formation in vivo. Digestion in vitro with trypsin or leukocyte elastase produces a polypeptide with similar structure and biological activity to globular adiponectin. To address how globular adiponectin is produced endogenously, we developed an assay that measures cleavage of recombinant adiponectin into globular adiponectin by serum. N‐terminal sequencing of globular adiponectin revealed proteolysis occurred at Gly‐93. It was also found that the protease exclusively required Ca2+ for activity and that had an apparent molecular mass of about 80 kDa by gel filtration chromatography. The enzyme was insensitive to an inhibitor of leukocyte elastase, but was inhibited by hirudin and argatroban, specific inhibitors of thrombin. Our data indicate that thrombin likely mediates formation of globular adiponectin in the circulation. Supported by Canadian Institutes for Health Research.