A Pericellular Collagenase Directs the 3-Dimensional Development of White Adipose Tissue

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 und...

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Bibliographic Details
Published in:Cell 2006-05, Vol.125 (3), p.577-591
Main Authors: Chun, Tae-Hwa, Hotary, Kevin B., Sabeh, Farideh, Saltiel, Alan R., Allen, Edward D., Weiss, Stephen J.
Format: Article
Language:English
Subjects:
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
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Summary: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.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2006.02.050