”Master switch” for ”good” fat may harbour obesity cure

August 21st, 2008 - 12:53 pm ICT by ANI  

London, Aug 21 (ANI): Researchers at Dana-Farber Cancer Institute have identified a long-sought ”master switch” in mice for the production of calorie-burning brown fat, which raises the prospect of new ways to fight obesity and overweight.
A team led by Dana-Farber’’s Bruce Spiegelman, PhD, demonstrated that brown fat - known as the ”good” form of fat because it burns calories and releases energy, unlike ”bad” white fat that simply stores extra calories - can be generated from unspecialised precursors that routinely spawn skeletal muscle.
The researchers 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.
He said that the ”huge surprise”of the study results 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.
He said that the confirmation would spur ongoing research in his laboratory, 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 might be to transplant brown fat cells into an overweight person to turn on the calorie-burning process, he added.
“I think we now have very convincing evidence that PRDM16 can turn cells into brown fat cells, with the possibility of combating obesity,” Nature quoted Spiegelman, as saying.
Spiegelman and colleagues reported that 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.
Spiegelman said that the PRDM16 trigger ”is very powerful at what it does”.
The study is published in the Aug. 21 issue of the journal Nature. (ANI)

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