A pericellular collagenase directs the 3-dimensional development of white adipose tissue

Cell. 2006 May 5;125(3):577-91. doi: 10.1016/j.cell.2006.02.050.


White adipose tissue (WAT) serves as the primary energy depot in the body by storing fat. During development, fat cell precursors (i.e., preadipocytes) undergo a hypertrophic response as they mature into lipid-laden adipocytes. However, the mechanisms that regulate adipocyte size and mass remain undefined. Herein, we demonstrate that the membrane-anchored metalloproteinase, MT1-MMP, coordinates adipocyte differentiation in vivo. In the absence of the protease, WAT development is aborted, leaving tissues populated by mini-adipocytes which render null mice lipodystrophic. While MT1-MMP preadipocytes display a cell autonomous defect in vivo, null progenitors retain the ability to differentiate into functional adipocytes during 2-dimensional (2-D) culture. By contrast, within the context of the 3-dimensional (3-D) ECM, normal adipocyte maturation requires a burst in MT1-MMP-mediated proteolysis that modulates pericellular collagen rigidity in a fashion that controls adipogenesis. Hence, MT1-MMP acts as a 3-D-specific adipogenic factor that directs the dynamic adipocyte-ECM interactions critical to WAT development.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / enzymology*
  • Adipogenesis / physiology
  • Adipose Tissue / cytology
  • Adipose Tissue / enzymology*
  • Adipose Tissue / growth & development*
  • Animals
  • Animals, Newborn
  • Cell Differentiation / genetics
  • Cell Enlargement
  • Collagen / metabolism
  • Collagenases / metabolism
  • Extracellular Matrix / enzymology*
  • Extracellular Matrix / genetics
  • Hypertrophy / enzymology
  • Matrix Metalloproteinase 14
  • Matrix Metalloproteinases / genetics*
  • Matrix Metalloproteinases, Membrane-Associated
  • Mice
  • Mice, Knockout
  • Stem Cells / cytology
  • Stem Cells / enzymology*


  • Mmp14 protein, mouse
  • Collagen
  • Collagenases
  • Matrix Metalloproteinases
  • Matrix Metalloproteinases, Membrane-Associated
  • Matrix Metalloproteinase 14