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Updated 11:00 AM May 8, 2006




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Expanding waistlines triggered by genes

A gene that degrades the body's collagen infrastructure has been shown to make fat cells fatter and expand girth, according to researchers at the Life Sciences Institute (LSI).

Excess fat is stored in white adipose tissue, the primary energy depot in the body, primarily around the midsection. The gene studied by a U-M team acts as a metabolic scissors, cutting through the collagen tissue web that holds fat in place and that allows fat cells to expand beneath the belly.

The collaborative research team, headed by LSI researchers Tae-Hwa Chun, Stephen Weiss and Alan Saltiel, discovered that the gene called membrane-type 1 matrix metalloproteinase (MT1-MMP) shears the collagen meshwork that holds fat cells in place and frees expanding fat cells, allowing their spread and expansion underneath the skin.

The study illustrates a relationship between the gene and obesity and metabolism.

The MT1-MMP gene specifically is important in regulation of fat cell size and metabolic gene expression. In an experiment with mice in which the gene was turned off, the animals became skinny. The fat tissues around their bellies were very small, but the brown adipose tissue—a specialized fat depot to regulate body energy consumption—was unaffected.

The team also discovered that fat cell differentiation in a two-dimensional laboratory cell culture is different from the three-dimensional (3-D) construction taking place inside a living animal. In a 2-D cell culture, the MT1-MMP gene was not necessary, but it becomes a critical metabolic scissors once cells are inside a 3-D environment. This finding may fill a gap between conventional 2-D cell biology and 3-D tissue function.

The findings shed new light on fat cell biology and could provide novel therapeutics to prevent the progression of obesity. The researchers will continue to work on the cellular mechanism of obesity and metabolic diseases from the perspective of 3-D cell biology.

The paper, "A Pericellular Collagenase Directs the 3-Dimensional Development of White Adipose Tissue," was published in the May 5 issue of Cell.

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