Adipocyte produces matrix metalloproteinases 2 and 9 - Involvement in adipose differentiation

Adipocyte hypertrophy and hyperplasia together with angiogenesis contribute to the growth of the fat mass. Because changes in the extracellular matrix (ECM) components are often associated with such cellular remodeling, we st udied the adipocyte expression of the matrix metalloproteinases (MMPs) 2 an d 9, two key enzymes involved in the modulation of ECM. The present study p rovides the first evidence that human adipose tissue produces and secretes MMP-2 and -9 as shown by gelatin zymography analysis performed on media con ditioned by human subcutaneous adipose tissue and human preadipocytes in pr imary cultures and by reverse transcriptase-polymerase chain reaction (RT-P CR) analysis on transcripts from mature human adipocytes. The further chara cterization performed on the murine 3T3F442A preadipocyte cell line demonst rates that MMP expression, assessed by RT-PCR and Western blot analysis, as well as activity, assessed by gelatin zymography analysis, increased durin g the adipocyte differentiation, whereas the expression of tissue inhibitor metalloproteinases I and 2 were abolished or not affected, respectively. F inally, preadipocyte treatment with MMP inhibitors such as batimastat and c aptopril, as well as neutralizing antibodies, markedly decreased adipocyte differentiation as demonstrated by the inhibition in the appearance of lipo genic (triglycerides) and lipolytic (glycerol release and hormone-sensitive lipase expression) markers. These data suggest that MMP-2 and -9 could be important key regulators of adipocyte differentiation. Thus, the adipocyte- derived MMPs might represent a new target for the inhibition of adipose tis sue growth.