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Keywords:

Adipose Tissue, Animals, Dietary Fats, Disease Models, Animal, Enzyme Precursors, Gelatinases, Histocytochemistry, Hypertrophy, Matrix Metalloproteinase 2, Matrix Metalloproteinase 9, Mice, Mice, Obese, Microscopy, Electron, Obesity, RNA, Messenger, Science & Technology, Life Sciences & Biomedicine, Hematology, Peripheral Vascular Disease, Cardiovascular System & Cardiology, obesity, matrix metalloproteinases, gelatinase, PLASMINOGEN-ACTIVATOR INHIBITOR-1, MATRIX-METALLOPROTEINASE, TARGETED INACTIVATION, CELL-DIFFERENTIATION, VASCULAR-DISEASE, DEFICIENT MICE, GROWTH-FACTOR, FAT CELLS, ADIPOCYTE, SYSTEM, 1102 Cardiorespiratory Medicine and Haematology, 1103 Clinical Sciences, Cardiovascular System & Hematology, 3201 Cardiovascular medicine and haematology, 3202 Clinical sciences

Abstract:

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 have 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 kept on SFD; gonadal and subcutaneous fat pads were removed and analysed ex vivo. 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 mice on HFD; 3) the contribution of active MMP-2 to the total level was comparable in SFD and HFD groups (20 to 30%); and 4) gelatinase B (MMP-9) was not consistently detected. These findings were confirmed by gelatin zymography and by mRNA determination using competitive RT-PCR. The presence of MMP-2 in the adipose tissue was confirmed immunologically and its localization in adipocytes revealed by immunogold electron microscopy. The potential functional role of MMP-2 in adipose tissue remains to be determined.