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Researchers identifiy mechanism that turns white fat cells to brown


August 6, 2012

The identification of the mechanism that causes white fat cells to become brown fat cells could lead to new treatments for obesity and type-2 diabetes (Photo: Shutterstock)

The identification of the mechanism that causes white fat cells to become brown fat cells could lead to new treatments for obesity and type-2 diabetes (Photo: Shutterstock)

Earlier this year, a team from UC San Francisco reported on the discovery that a class of commonly prescribed type-2 diabetes drugs, called TZDs (thiazolidinediones, such as Actos and Avandia), promoted the conversion of energy-storing white fat cells into energy-burning brown fat cells. Now researchers at Columbia University Medical Center (CUMC) have identified the mechanism that causes this change to take place, potentially leading to new treatments for obesity and type-2 diabetes.

While it was known that TZDs have the ability to change white fat cells to brown fat cells by activating a cell receptor called peroxisome proliferator-activated receptor–gamma (ppar-gamma), the exact mechanism behind this transformation was unclear. Because TZDs have numerous adverse side effects, including liver toxicity, bone loss and, surprisingly enough, weight gain, the CUMC researchers, led by Domenico Accili, MD, professor of Medicine and the Russell Berrie Foundation Professor at CUMC, were attempting to find a safer way to change white fat to brown fat.

Having previously shown that increasing the activity of a group of enzymes called sirtuins (or Sir2) in mice resulted in increased metabolic activity, the CUMC team has now shown that this boost in metabolism is a result of promoting the browning of white fat.

“When we sought to identify how sirtuins promote browning, we observed many similarities between the effect of sirtuins and that of TZDs,” said lead author Li Qiang, PhD, associate research scientist in Medicine at CUMC.

Knowing that sirtuins work by severing the chemical bonds between acetyl groups and proteins in a process known as deacetylation, the researchers wanted to uncover whether sirtuins remove acetyl groups from ppar-gamma and if this deacetylation of ppar-gamma is crucial to the browning of white fat. They confirmed this is the case by creating a mutant gene of ppar-gamma that, in effect, mimicked the actions of sirtuins and promoted the development of brown fat-like qualities in white fat cells in both mice and human fat tissue.

“Our findings have two important implications,” said Dr. Accili. “First, they suggest that TZDs may not be so bad – if you can find a way to tweak their activity. Second, one way to tweak their activity is by using sirtuin agonists – that is, drugs that promote sirtuin activity.”

“The truth is, making sirtuin agonists has proved to be a real bear – more promise than fact,” he continued. “But now, for the first time, we have a biomarker for good sirtuin activity: the deacetylation of ppar-gamma. In other words, any substance that deacetylates ppar-gamma should in turn promote the browning of white fat and have a beneficial metabolic effect.”

The CUMC team’s findings appear in the online edition of the journal Cell.

Source: CUMC

About the Author
Darren Quick Darren's love of technology started in primary school with a Nintendo Game & Watch Donkey Kong (still functioning) and a Commodore VIC 20 computer (not still functioning). In high school he upgraded to a 286 PC, and he's been following Moore's law ever since. This love of technology continued through a number of university courses and crappy jobs until 2008, when his interests found a home at Gizmag. All articles by Darren Quick

Weight loss pills that really work permanently would be real nice.


A pill may be fine to reduce fat, but peoples eating and life style choices won't change if there is a quick fix. All people in 1st and 2nd world countries, over eat. We are the only animal on earth that is so complacent, we become obese, secondary diseases then illness then death all because we eat, way too much. someone will make squillions out of this and that is the real killer. Big corporates with crap food make people fat and ill, then they invest in a cure, and if that does not work for the individual, then invest in a funeral home:)

Paul Perkins

Micheal Phelps consumes 10000 calories from McDonalds food on a training day and he stays fit. People have a lot to learn on how to burn those calories by "really" moving around. We weren't made to be couch potatoes.

Fretting Freddy the Ferret pressing the Fret

Freddy that's fine for those freely able to exercise. However, there are those like myself who are overweight through no real fault of our own. I have five or six damaged discs, ongoing spinal degeneration, peripheral neuropathy and various other gems. I see a pain management doctor monthly and take a host of medications. A pill that could help shed weight would be nothing short of a miracle. 

Matthew Fagan

Michael Phelps does not burn 10K calories though. 4 hours of swimming cannot burn the excess of 7-8K calories. A calorie is not a calorie and The first law of thermodynamics is totally misinterpreted by most nutritionists. Read Gary Taubes! And eating more and then burning it is ridiculous and unhealthy. Fast metabolism leads to faster death, too, as metabolism and exercise are toxic. People need to get familiar with basic biology and understand the consequences of the Hayflick limit and try to slow metabolism (including basal) and not be tricked into doing the the opposite by various billion-dollar industries. Neil Armstrong has once said: "I believe that every human has a finite number of heartbeats. I don't intend to waste any of mine running around doing exercises."

Nikolay Kolev
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