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Scientists Reprogram Fat Cells to Increase Fat Burning


Scientists have now discovered how fat cells can be reprogrammed to burn fat instead of storing it. By analyzing molecular processes, scientists have described for the first time how white fat cells are converted into brown fat cells.


Cells responsible for storing 1) ___ can be converted into cells that burn fat and keep you thinner and healthier. Scientists have now discovered how this conversion happens. “We’ve mapped the fat cells’ genomes and identified a protein which activates specific 2) ___ that reprogram the fat cells to burn fat instead of storing it,“ says Professor S. Mandrup from the department of biochemistry and molecular biology at the University of Southern Denmark (SDU). The study’s findings, recently published the January 2015 journal, Genes & Development, are a crucial step on the way to developing 3) ___ that can make the body transform fat into energy instead of storing it.


Our body contains three different types of fat cells: White cells, which store fat derived from food so that you put on weight if you eat too much; 4) ___ fat cells, which convert fat into energy instead of storing it; Brite fat cells are beige/brownish in color (brite is short for brown-in-white). Like brown cells they convert fat into heat. Scientists have long been interested in brite fat cells because it has been shown that white fat cells can be browned and turned into brite so that they burn fat instead of storing it. Studies show that overweight people have a lot of white cells in their fatty 5) ___. We’ve known for a long time that exposure to the cold, for example, can cause the body to produce more brite fat cells which produce heat, although we have not known much about which molecular mechanisms are at play.


Anti-Diabetic Medication Browns Cells

In order better to understand how fat-storing white cells can become fat-burning brite cells, scientists at SDU have grown white cells in the laboratory and added a medication previously used to increase the insulin sensitivity of 6) ___ patients. The medication known as rosiglitazone (Avandia) makes the fat cells turn brown thus making them brite — but exactly what effect the drug has on the cells at the molecular level has been unclear until now. To study this, the scientists used advanced gene sequencing technology to map and analyze the genome of both the white and brite cells in order to find out which genes are active when the 7) ___ cells turn brite.


A Specific Protein Activates Genes

Their analyses did not only show where in the fat cells’ genome there is activity when white cells are converted to brite cells, but also that a specific 8) ___, known as KLF11, has to be present for the cells to be reprogrammed to burn fat instead of storing it. It’s clear that KLF11 finds the genes in the cells which are active when white fat cells are being converted into brite cells. KLF11 is already known as a protein important to the functionality of insulin-producing beta-cells in the pancreas, but with our study we have demonstrated, for the first time that the protein is also necessary for white fat cells to be reprogrammed to brite fat cells.


White fat cells have been known about for many years, but it was not until 2009 that scientists discovered that adult human beings also have so-called brown fat tissue. The fatty tissue is referred to as brown because of its reddish-brown color when viewed through a microscope. The brown color occurs because the cells contain many mitochondria and 9) ___ vessels. Over the past decade it was also discovered that humans have brite fat cells. Brite fat cells burn fat just like the brown ones. In other words: the more brite and brown fat cells you have the more 10) ___ you burn. Unlike the entirely brown fat cells, brite cells are produced from already-existing white fat tissue of the kind we have most of in our body. Scientists still have a lot to learn about brite fat cells. They do not know, for instance, whether we can cause more brite fat cells to be produced, e.g. by eating specific foods. It is not known, either, whether brite cells can only be produced by converting white cells, or whether the body can produce its own new brite fat cells. In the long term, it will be possible to use the discovery to develop new medication which can impact on precisely those areas in the fat cells’ genome. This will make it possible to prevent overweight people from developing insulin intolerance and diabetes or other diseases related to 11) ___. We know more about which buttons we have to push to increase specific processes in the cells which activate the browning process. KLF11 is just one of the factors that determines which genes are active, researchers are certain there are many others.


Jacob B. Hansen, an associate professor at the Department of Biology of the University of Copenhagen, who studies brown fat cells, says that the new results represent an important step towards understanding how fat cell conversion takes place in humans. The molecular understanding of how brite is produced and much of what we do know comes from experiments on mice, however, this study is entirely based on 12) ___ cell material. Experiments on mice have shown that KFL11 can regulate parts of the biology of brown fat cells, but in this study, the scientists used advanced methods which enabled them to characterize the browning process in great detail. This was much more elegant than the work previously done on mice because they’ve observed all the genes in one go and found the areas in the genome of the cells which KLF11 binds to. Pills against obesity are closer to reality. The result certainly is a step in the direction of a cure which e.g. can reduce the risk of people developing type 2 diabetes and countering other health issues related to being overweight. The potential is interesting, because the better we understand the biology of fat cells, the closer we’ll get to being able to design medication which can cause the body to produce more beige and brown fat cells, which experiments on mice have shown effective to improve glucose tolerance. “But this doesn’t mean that in five years will have a magic pill against obesity,“ Hansen says. “The work done at SDU is basic science, which improves our knowledge of the process known as browning, but a lot more research will have to be done before we fully understand the process and its significance.“ The genome of white adipocytes, has been investigated and is reprogrammed during browning using advanced genome sequencing technologies. Browning has been stimulated in human white adipocytes by a drug used to treat type II diabetes and compared to white and “brite“ fat cells. This comparison showed that 13) ___ fat cells have distinct gene programs which, when active, make these cells particularly energy-consuming. By identifying the areas of the genome that are directly involved in the reprogramming, an important factor has been identified in the process — the gene regulatory protein KLF11 (Kruppel Like Factor-11), which is found in all fat cells, is required for the reprogramming to take place. This research has been a long process, taking four years to get the results being published. The discovery of the “brite“ fat cell mechanisms and the specific regulatory areas brings scientists closer to understanding how reprogramming of white fat cells takes place. This knowledge potentially means, that in the future drugs can be 14) ___to activate the genomic regions and browning factors like KLF11 in the treatment of obesity.


ANSWERS: 1) fat; 2) genes; 3) drugs; 4) brown; 5) tissue; 6) diabetes; 7) white; 8) protein; 9) blood; 10) energy; 11) obesity; 12) human; 13) “brite“; 14) targeted



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