Watch Online the Live Sessions of ISWWTA 2015 Rishikesh on Youtube.Visit:
Previous issues of AYUSH DARPAN in Hindi is now available online visit:

Search Engine

Tuesday, 10 July 2012

Molecule Identified That Makes Fat Cells Fatter

A group of scientists at the University of Michigan carried out a study to understand why the fat-storing cells get fatter and takes a long time to metabolize fat in obese individuals.
Obesity is a fast becoming a world –wide phenomenon and the morbidity and mortality burden due to obesity is increasing globally at an alarming rate.
Ormond MacDougald and his colleagues tried to study the signals sent by fat-storing cells to each other in their effort to understand why fat cells get fatter and how people become obese.
In an array of experiments carried out on mice, the researchers revealed the presence of a molecule called Sfrp5. They showed that this molecule  influences a signaling pathway known as WNT, stimulates the adipocytes (fat cells) to grow bigger and larger and suppress the rate at which fat is metabolized in the mitochondria of fat cells.
By preventing the adipose cells from producing Sfrp5, the researchers were able to prevent the mice from becoming fat quite so quickly. Despite being fed on high-fat diet, the adipocytes in these mice didn't grow large.
The research was carried out with NIH funding in the U-M Medical School laboratory of Ormond MacDougald, Ph.D., in the Department of Molecular & Integrative Physiology. The team had realized the importance of WNT signaling in fat cell development through their previous work.
"WNT signaling plays a crucial role in regulating, and inhibiting, white fat cell growth and the recruitment of new cells to store fat," MacDougald explains. "But it appears that in obesity, Sfrp5 can interfere with that signaling, and may create a feedback loop that keeps stimulating production of more of itself."
MacDougald and his team began to zero in on the molecule Sfrp5 after several years of observing WNT signaling between adipocytes. It was observed by several groups of researchers that the amounts of Sfrp5 generated in fat tissues of obese animals were much higher.
Initially, when they bred mice that could not produce the Sfrp5, they expected to see non-obese mice that resisted obesity due to their inability to convert more cells into adipocytes and thereby store fat. But what they found was that the mice without the molecule had as many fat cells as those with the molecule, but they came with a difference – the adipocytes in the former did not grow bigger and accumulate fat.These mice did not become fat no matter how calorie- laden their diet was.
Another feature of these Sfrp5-deficient mice was that the mitochondrial genes inside the adipose cells registered a surge of activity, as a result of which fat was easily burned down for the cell’s activities. It was as if the ‘mitochondrial furnaces’ began to work over time in the absence of these molecules.
"From our results, we believe that Sfrp5 is an important moderator of mitochondrial activity-- the first time this has been seen for the WNT signaling pathway in adipocytes," says Mori the lead author of the study "This underscores the complexity of WNT signaling," mori adds.
 A look into the underlying mechanism reveals that Sfrp5 works as a decoy receptor to which WNT signals bind. This prevents them from binding to the cell surface receptors that they would otherwise bind to. When the WNT signaling is reduced, the adipose cells grow larger and don’t burn fat that easily. The cells grow larger to store the accumulated fat. Then, a feedback loop is created and the cells produce more Sfrp5, creating the tendency for adipocytes to accumulate more lipid.
It may be possible for anti-obesity drugs to target the signalling pathway but, MacDougald warns that more experiments need to be carried out in mice and humans before going down the drug trail. With the world in the grip of obesity, and its related health conditions, this field of research demands immediate attention.
Mori et al; Journal of Clinical Investigation (online) 2012; July issue 


No comments:

Post a comment

Facebook Badge