Matrix Metalloproteinase Inhibition Affects Adipose Tissue Mass in Obese Mice

Clin Exp Pharmacol Physiol. 2012 Jun;39(6):544-50. doi: 10.1111/j.1440-1681.2012.05714.x.

Abstract

1. 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. 2. 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. 3. 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. 4. 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). 5. Thus, the relatively gelatinase-specific MMP inhibitor tolylsam has the potential to affect fat tissue growth in obese mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / enzymology*
  • Adipose Tissue / pathology
  • Animals
  • Body Weight / drug effects
  • Body Weight / physiology
  • Diet, High-Fat* / methods
  • Male
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 9 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Obesity / drug therapy
  • Obesity / enzymology*
  • Oxadiazoles / pharmacology*
  • Oxadiazoles / therapeutic use
  • Sulfonamides / pharmacology*
  • Sulfonamides / therapeutic use

Substances

  • 3-methyl-2-(4-(3-p-tolyl(1,2,4)oxadiazol-5-yl)benzenesulfonylamino)butyric acid
  • Oxadiazoles
  • Sulfonamides
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9