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In 3D, early fat development first requires 'remodeling'

In the May 5, 2006 Cell, researchers report the serendipitous discovery that the initial development of fat requires a "remodeling" protein that must first make way for the lipid-laden tissue's growth. An enzyme that "chews" through collagen fibers sculpts the matrix surrounding fat cells, allowing them to expand and mature, the team reports.

In the absence of the collagen-busting "membrane-anchored metalloproteinase" (MT1-MMP), would-be fat cells, or preadipocytes, fail to break through the fibrous extracellular matrix, they found. Moreover, the cells entrapment within a dense collagen meshwork disrupts their structure. That structural change, in turn, stalls the genetic programs critical for full-blown fat development, leading to sweeping changes in gene activity.

In contrast, they report, fat cells deficient for MT1-MMP develop apparently normally when placed on the flat surface of a laboratory dish.

"When small fat cells embedded in what is essentially a 3D molecular cage receive the appropriate external signals during development, it appears that they change their geometry--remodeling the surrounding matrix using an enzyme to chew the fibers," said the study's senior author Stephen Weiss of the University of Michigan, Ann Arbor.

For reasons that are not entirely clear, that shape change leads to a dramatic shift in gene expression and cell behavior, he added. In the absence of the collagen-rich 3-dimensional matrix, the MT1-MMP enzyme apparently becomes irrelevant.

The study identifies MT1-MMP as a "heretofore unsuspected 3-dimensional matrix specific regulator of white adipose tissue development and function," the researchers said. White adipose tissue is a type of fat that serves as a primary depot for energy stores.

Moreover, the findings in developing mice raise the possibility that the enzyme might also play an important role in the remodeling of extracellular barriers in adult animals as they gain or burn f
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Contact: Heidi Hardman
hhardman@cell.com
617-397-2879
Cell Press
4-May-2006


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