In:
eLife, eLife Sciences Publications, Ltd, Vol. 3 ( 2014-08-27)
Abstract:
The growing rates of obesity and related metabolic diseases are a major public health concern worldwide. People who are overweight or obese are at increased risk for a range of diseases including diabetes and heart disease, which may reduce their quality of life and shorten their lifespans. Obese people have more, larger fat cells than individuals of healthy weight, and so understanding how the body creates fat cells may provide new insights into ways to prevent or treat obesity. Fat cells arise from a population of stem cells that can also give rise to bone cells and cartilage. Some of the proteins—called transcription factors—that work together to turn on the expression of genes needed for a stem cell to become a fat cell have been identified. However, the exact regulatory processes that cause an unspecialized cell to develop into a fat cell remain unclear. Gubelmann et al. set out to identify more of the transcription factors that cause stem cells to become fat cells. A high-throughput, automated process was used to test the effect of over-expressing each of 734 transcription factors in mouse cells that are primed to become fat cells. Twenty-six transcription factors were found to increase the number of these primed cells that became mature fat cells—most of which had not previously been shown to affect how fat cells develop. The most powerful driver of fat cell development was ZEB1: a transcription factor that has previously been implicated in many other biological processes. Most notably, ZEB1 was linked to a transition during development that allows cells to migrate to the correct location in the embryo, but also to a mechanism that allows cancerous cells to spread to new tissues. Using studies of mouse cells and live mice, computational analyses, and biopsies from obese patients, Gubelmann et al. show that ZEB1 regulates numerous other transcription factors that promote the development of fat cells. These include factors that initially set an unspecialized cell on the path to becoming a fat cell and those that guide the changes that occur as the fat cell matures. Further studies will be required to show whether the ZEB1 protein itself is needed to prime stem cells to start becoming fat cells.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.03346.001
DOI:
10.7554/eLife.03346.002
DOI:
10.7554/eLife.03346.003
DOI:
10.7554/eLife.03346.004
DOI:
10.7554/eLife.03346.005
DOI:
10.7554/eLife.03346.006
DOI:
10.7554/eLife.03346.007
DOI:
10.7554/eLife.03346.008
DOI:
10.7554/eLife.03346.009
DOI:
10.7554/eLife.03346.010
DOI:
10.7554/eLife.03346.011
DOI:
10.7554/eLife.03346.012
DOI:
10.7554/eLife.03346.013
DOI:
10.7554/eLife.03346.014
DOI:
10.7554/eLife.03346.015
DOI:
10.7554/eLife.03346.016
DOI:
10.7554/eLife.03346.017
DOI:
10.7554/eLife.03346.018
DOI:
10.7554/eLife.03346.019
DOI:
10.7554/eLife.03346.020
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2014
detail.hit.zdb_id:
2687154-3
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