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Matrix metalloproteinase inhibition affects adipose tissue mass in obese mice
Author(s) -
Hul Matthias,
Lupu Florea,
Dresselaers Tom,
Buyse Johan,
Lijnen H Roger
Publication year - 2012
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2012.05714.x
Subject(s) - adipose tissue , endocrinology , medicine , matrix metalloproteinase , gelatinase , chemistry , extracellular matrix , tissue inhibitor of metalloproteinase , adipose tissue macrophages , white adipose tissue , biology , biochemistry
Summary Because the development of adipose tissue involves remodelling of the extracellular matrix ( ECM ), which requires matrix metalloproteinase ( MMP ) activity, we examined whether MMP inhibitors may have the potential to affect adipose tissue mass in obese mice. Administration of the relatively gelatinase‐specific MMP inhibitor tolylsam (( R )‐3‐methyl‐2‐[4‐(3‐p‐tolyl‐[1,2,4]oxadiazol‐5‐yl)‐benzenesulphonylamino]‐butyric acid; 100 mg/kg per day) for 7 weeks to obese wild‐type mice on a high‐fat diet resulted in significantly lower bodyweight ( P < 0.05), lower subcutaneous ( SC ) and gonadal ( GON ) adipose tissue mass (both P < 0.05) and smaller adipocytes in both SC ( P < 0.005) and GON ( P < 0.0005) adipose tissues. Magnetic resonance imaging confirmed a lower total body fat content in tolylsam‐treated mice ( P < 0.0005). In addition, tolylsam treatment of wild‐type mice was associated with a marked enhancement in metabolic rate. Electron microscopy analysis of tissue sections at the end of the 7 week feeding period revealed significantly higher collagen accumulation in the ECM of SC adipose tissues of tolylsam‐treated mice ( P < 0.001). Thus, the relatively gelatinase‐specific MMP inhibitor tolylsam has the potential to affect fat tissue growth in obese mice.