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A fat cell grows up
Date:5/17/2010

PHILADELPHIA Getting from point A to B may sound simple, but not so in the formation of fat cells.

In a finding with potential drug-development implications, Mitchell A. Lazar, M.D., Ph.D., director of the Institute for Diabetes, Obesity, and Metabolism at the University of Pennsylvania School of Medicine, and colleagues report in the current issue of Genes & Development the discovery of an intermediate state between early-stage fat cells and fully mature ones that is only present transiently during the fat-cell formation process. This intermediate state is induced by hormones related to cortisol, which are known to contribute to obesity and metabolic disturbances in people.

New therapies for obesity or metabolic diseases such as diabetes could potentially target this transition state toward a maturing fat cell.

The transition state present within 24 hours of the start of the fat-cell differentiation process is defined by chemical changes to genetic material called chromatin, which package a cell's DNA. These changes kick start the expression of regulatory proteins and provide a cellular memory that allows the cell to continue developing even after the signal to undergo this transition has waned.

Probing the Genome

Like all cells in the body, fat cells arise from stem cells. Embryonic stem cells give rise to another type of stem cell, which in turn gives rise to early-stage fat cells. Upon stimulation, those early cells complete their differentiation to become fully mature fat cells. Lazar and his team asked: What are the molecular players required to induce the final transformation?

Using a cell culture system, the team, led by postdoctoral researcher David Steger, PhD, probed genes involved in fat-cell development and function for chromatin changes that were associated with the start of mature fat-cell formation. They found chromatin changes near a gene encoding the master regulator of d
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

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