Modulation of Adipose Tissue Expression of Murine Matrix Metalloproteinases and Their Tissue Inhibitors With Obesity
- 1Center for Molecular and Vascular Biology, University of Leuven, Belgium
- 2Laboratory of Tumor and Development Biology, University of Liège, Belgium
- 3Laboratory of Biology of Connective Tissues, University of Liège, Belgium
Abstract
The potential role of the matrix metalloproteinase (MMP) system in the pathophysiology of the adipose tissue was investigated in a mouse model of nutritionally induced obesity. mRNA levels of 16 MMPs and 4 tissue inhibitors of MMPs (TIMPs) were measured by semiquantitative RT-PCR in adipose tissue isolated from mice maintained for 15 weeks on a standard or high-fat diet. In mice on standard diet, with the exception of MMP-8, all MMP and TIMP transcripts were detected in both gonadal and subcutaneous depots. In obese mice, the expression of MMP-3, -11, -12, -13, and -14 and TIMP-1 mRNAs was upregulated, whereas that of MMP-7, -9, -16, and -24 and TIMP-4 was downregulated. Most MMP and TIMP mRNAs were expressed at higher levels in stromal-vascular cells than in mature adipocytes. Analysis of adipose tissue by in situ fluorescent zymography revealed MMP-dependent proteolytic activities, demonstrating the presence of active MMPs in the intact tissue. In vitro conversion of adipogenic 3T3-F442A cells into mature adipocytes was associated with substantial modulations of MMP and TIMP expression. Moreover, this in vitro adipogenesis was reduced in the presence of a synthetic MMP inhibitor. Thus, the adipose tissue expresses a large array of MMPs and TIMPs, which modulate adipocyte differentiation.
Footnotes
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Address correspondence and reprint requests to H.R. Lijnen, Center for Molecular and Vascular Biology, University of Leuven, Campus Gasthuisberg, O & N, Herestraat 49, B-3000 Leuven, Belgium. E-mail: roger.lijnen{at}med.kuleuven.ac.be.
Received for publication 7 September 2001 and accepted in revised form 8 January 2002.
DMEM, Dulbecco’s modified Eagle’s medium; ECM, extracellular matrix; GPDH, glycerophosphate dehydrogenase; HFD, high-fat diet; KRBB, Krebs-Ringer bicarbonate buffer; MMP, matrix metalloproteinase; PAI-1, plasminogen activator inhibitor-1; PPAR, peroxisome proliferator-activated receptor; SFD, standard-fat diet; S-V, stromal-vascular; T3, triiodothyronine; TIMP, tissue inhibitor of MMP.
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