Making 'Good' Fat From Muscle And Vice Versa

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Making 'Good' Fat From Muscle And Vice Versa

http://medicalnewscenter.com/out/out.cgi?

http://www.sciencedaily.com/releases/2008/08/080820162852.htm

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 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.

Other authors of the paper include Bjork, PhD, and R.

Beier, PhD, MD, of Brigham and Women's Hospital; Rudnicki,

PhD, of the Ottawa Health Research Institute; and Hediye Erdjument-

Bromage, PhD, and Tempst, PhD, of Memorial Sloan-Kettering

Cancer Center.