Expanding waistlines triggered by your genes

A gene that degrades the body’s collagen infrastructure has been shown to make fat cells fatter and expand girth.

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

The collaborative research team, headed by researchers Tae-Hwa Chun, Stephen Weiss, and Alan Saltiel at U-M’s Life Sciences Institute (LSI), discovered that the gene 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 is specifically important in regulation of fat cell size and metabolic gene expression. When the gene function was deleted, mice 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.

Importantly, the research team also discovered that adipocyte differentiation in conventional two-dimensional (2-D) cell culture is different from three-dimensional (3-D) microenvironment taking place inside the complex body. In regular 2-D culture system, the MT1-MMP gene was not necessary, but it becomes a critical metabolic scissors once cells are inside 3-D environment either in collagen gel or in the real tissue of mouse. This finding may fill a gap between conventional 2-D cell biology and 3-D tissue function.

These findings shed new light on adipocyte biology and possibly will 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.