Adipose tissue expression of gelatinases in mouse models of obesity

Following the observation by Brown et al. (Am J Physiol 1997: 272: C937-49) that primary rat adipocytes in culture secrete gelatinase A (MMP-2), we ha ve evaluated gelatinase expression in adipose tissue with the use of mouse models of obesity. Wild-type mice were kept on a standard fat diet (SFD) or on a high Fat diet (42% fat, HFD) and genetically obese db/db mice were ke pt on SFD: gonadal and subcutaneous fat pads were removed and analysed ex v ivo, These studies revealed that: 1)the HFD induced adipocyte hypertrophy: 2) after 32 weeks. significantly higher levels of 70 kDa (p < 0.05) and 65 kDa proMMP-2 (p < 0.01) were observed in extracts of gonadal fat pads of mi ce on HFD; 3) the contribution of active MMP-2 to the total level was compa rable in SFD and HFD groups (20 to 30%): and 4) gelatinase B (MMP-9) was no t consistently detected. These findings were confirmed by gelatin zymograph y and by mRNA determination using competitive RT-PCR. The presence of MMP-2 in the adipose tissue was confirmed immunologically and its localization i n adipocytes revealed by immunogold electron microscopy. The potential func tional role of MMP-2 in adipose tissue remains to be determined.