Molecular switch found in mice could lead to future obesity treatments

Aug 20, 2008

A surprise discovery -- that calorie-burning brown fat can be produced experimentally from muscle precursor cells in mice -- raises the prospect of new ways to fight obesity and overweight, say scientists from Dana-Farber Cancer Institute.

Reporting in the Aug. 21 issue of the journal Nature, the researchers demonstrated that brown fat, which is known as the "good" form of fat -- so called because it burns calories and releases energy, unlike "bad" white fat that simply stores extra calories -- can be generated from unspecialized precursors that routinely spawn skeletal muscle.

The team led by Dana-Farber's Bruce Spiegelman, PhD, showed that a previously known molecular switch, PRDM16, regulates the creation of brown fat from immature muscle cells. They also determined that the process is a two-way street: Knocking out PRDM16 in brown fat cells can convert them into muscle cells. However, Spiegelman called the latter an "experimental lab trick" for which he currently envisions no practical applications.

The "huge surprise" of the study results, he said, was that muscle precursor cells known as "satellite cells" are able to give birth to brown fat cells under the control of PRDM16.

Spiegelman said the finding confirms that PRDM16 is the "master regulator" of brown fat development. The confirmation will spur ongoing research in his laboratory, he said, to see if drugs that rev up PRDM16 in mice -- and potentially, in people -- could convert white fat into brown fat and thereby treat obesity. Another strategy, he said, might be to transplant brown fat cells into an overweight person to turn on the calorie-burning process.

"I think we now have very convincing evidence that PRDM16 can turn cells into brown fat cells, with the possibility of combating obesity," said Spiegelman, the senior author of the paper. The lead author is Patrick Seale, PhD, a postdoctoral fellow in the Spiegelman lab.

Another paper in the same issue of Nature described a different trigger of brown fat production, a molecule called BMP7. A commentary in the journal by Barbara Cannon, an internationally recognized researcher in the biology of fat cells at the University of Stockholm, said that the two reports "take us a step closer to the ultimate goal of promoting the brown fat lineage as a potential way of counteracting obesity."

The Spiegelman group has long studied fat cells both as a model for normal and abnormal cell development, which relates to cancer, and also because fat cells play such a key role in the growing epidemics of obesity and diabetes.

There is much interest in brown fat's role in regulating metabolism. Rodents and human infants have abundant brown fat that dissipates food energy as heat to protect against the cold. Though human adults have little brown fat, it apparently does have a metabolic function, including the potential to be amplified in some way to combat obesity.

In 2007, Spiegelman and colleagues reported they had inserted PRDM16 genes into white fat precursors, which they implanted under the skin of mice. The PRDM16 switch coaxed the white fat precursors to produce brown fat cells instead of white. To Spiegelman, this suggested the possibility of transplanting PRDM16-equipped white fat precursors into people who are at high risk of becoming obese, to shift their metabolism slightly into a calorie-burning mode.

The new research adds another potential source of brown fat -- the muscle cell progenitors, or myoblasts, that exist in the body to replace mature muscle cells as needed. The progenitors, which can be thought of as "adult stem cells," are committed to becoming specialized muscle cells when activated by appropriate signals, or, as the study revealed, brown fat cells when PDRM16 is turned on. The PRDM16 trigger "is very powerful at what it does," said Spiegelman, who is also a professor of cell biology at Harvard Medical School.

Source: Dana-Farber Cancer Institute

Explore further: Gamers helping in Ebola research

add to favorites email to friend print save as pdf

Related Stories

Knowing how brown fat cells develop may help fight obesity

Mar 14, 2013

Brown fat is a hot topic, pardon the pun. Brown fats cells, as opposed to white fat cells, make heat for the body, and are thought to have evolved to help mammals cope with the cold. But, their role in generating ...

Study identifies cells that give rise to brown fat

Dec 20, 2010

In some adults, the white fat cells that we all stockpile so readily are supplemented by a very different form of fat—brown fat cells, which can offer the neat trick of burning energy rather than storing it. Researchers ...

Brown fat cells make 'spare tires' shrink

Dec 01, 2009

(PhysOrg.com) -- Scientists at the University of Bonn have found a new signalling pathway which stimulates the production and function of so-called brown fat cells. They propose using these cells that serve as a "natural ...

New insight into stem cell development

May 22, 2014

The world has great expectations that stem cell research one day will revolutionize medicine. But in order to exploit the potential of stem cells, we need to understand how their development is regulated. Now researchers ...

Conversion from bad fat to good fat

Apr 28, 2013

Scientists from ETH Zurich in Switzerland have shown for the first time that brown and white fat cells in a living organism can be converted from one cell type to the other. Their work, using mice as a model organism, provides ...

Recommended for you

Gamers helping in Ebola research

14 hours ago

Months before the recent Ebola outbreak erupted in Western Africa, killing more than a thousand people, scientists at the University of Washington's Institute for Protein Design were looking for a way to stop the deadly virus.

Carcinogenic role of a protein in liver decoded

17 hours ago

The human protein EGFR controls cell growth. It has mutated in case of many cancer cells or exists in excessive numbers. For this reason it serves as a point of attack for target-oriented therapies. A study ...

A new way to diagnose malaria, using magnetic fields

Aug 31, 2014

Over the past several decades, malaria diagnosis has changed very little. After taking a blood sample from a patient, a technician smears the blood across a glass slide, stains it with a special dye, and ...

User comments : 0