The Origin of Fat Cells
September 13, 2005
ANN ARBOR, Mich.---A new study in the journal Cell Metabolism explains some crucial steps in how fat cells are formed. The findings may help in understanding chronic diseases, such as obesity and diabetes.
Research conducted in the laboratory of Alan Saltiel, Director of the UM Life Sciences Institute, dissected the genetic effects of a hormonal cocktail that induces the transition from fat-cell precursors to full-blown fat cells.
Like all cells, fat cells develop from stem cells. The fate of a stem cell is predetermined. Pre-fat cells are programmed to turn into fat cells when exposed to a certain hormonal environment. Saltiel's group looked at how the hormones affected that cellular change.
The process of adipocyte differentiation is accompanied by changes in the expression pattern of integrin receptors. In this issue, Liu et al. (pp. 165-177) show that alpha5 integrin (fibronectin receptor) functions to maintain Rac activity in preadipocytes. By contrast, alpha6 integrin (laminin receptor) downregulates Rho activity by mediating the clustering of growth-arrested cells prior to terminal differentiation. The cover image depicts an immunofluorescence staining showing the surface localization of integrin alpha6 (green) in mature 3T3-L1 adipocytes.
"The body needs fat cells. They serve as a storage depot for fuel as well as a sensor of hormone and energy status. These cells sense the amount of fat and secrete hormones that maintain energy balance throughout the body," said Saltiel.
We all need the right number of fat cells. Too many, big fat cells cause obesity, while too few cause a disease called lipodystrophy, where fat has to be stored in muscle or liver. Both problems can lead to diabetes.
Saltiel and his lab wanted to figure out how these hormones led to formation of fat cells, so withheld one ingredient in the cocktail, and then looked at all the genes that changed. Among the hundreds of genetic changes were two receptor proteins called integrins found on the surface of cells. Integrins bind to the extra-cellular matrix that surrounds the cell, and serve as switchboards to control the shape, size and growth of cells.
The crucial event occurred when integrin alpha 5 was decreased and integrin alpha 6 was increased. This "integrin switching" caused cells to stop growing, and cluster together, which ultimately led to changes in the shape of the cells.
"Fat cells require contact in order to stretch and change shape - becoming round enables the cell to accumulate lots of lipids," said Saltiel. "While many changes occur in the generation of fat cells, the transition from one integrin to another is a crucial step."
Saltiel believes the study could have implications in understanding obesity and diabetes, and opens the door to new explorations centered on how integrins control fat formation.
