A new treatment for obesity?

[Captain Picard's Hair]

http://www.nytimes.com/2009/07/30/science/30fat.html?hp

July 30, 2009
Discovery May Help Treat Obesity
By NICHOLAS WADE

A new approach to treating obesity has been opened up by a discovery about how the body creates brown fat, the cells that burn white fat and turn it into body heat.

Researchers led by Bruce M. Spiegelman of Harvard Medical School report their discovery in Thursday's issue of the journal Nature. Their paper describes the natural system by which brown fat cells are generated from their precursors.

Dr. Spiegelman has used this system - a pair of proteins that switch on the brown fat cell's distinctive genes - to convert both mouse and human skin cells into brown fat cells.

Brown fat cells have a very different role from the better-known white fat cells. The white cells store fat; the brown cells burn it off as heat.

Babies have lots of brown fat to help keep warm. Until April 2009, biologists believed that the brown fat quickly disappeared and was not found in adults. Dr. Sven Enerback of the University of Goteborg in Sweden and others then reported that some brown fat tissue persisted in adults, raising the possibility that if the cells could be made more active, a person might burn off more fat.

In a parallel line of research that has now converged with the brown fat discovery, Dr. Spiegelman has long being studying the body's white fat cells and how they are controlled. In 1994 he found the body's master regulator of white fat cells. Turning to brown fat cells, he followed the general assumption that they were derived from white fat cells.

A key element in making brown fat cells seemed to be a kind of protein called a zinc finger (because it reaches into the spiral of a DNA molecule to switch on particular genes). Dr. Spiegelman figured that if he inactivated all the relevant zinc finger proteins in brown fat cells, they should turn back into their precursors, the white fat cells.

The experiment worked. The brown fat cells did revert, but not into white fat cells. They turned into muscle cells.

"It was the most bizarre experiment my lab ever did," Dr. Spiegelman said Wednesday.

His discovery that muscle cells are the natural precursors of brown fat cells was made last year. Dr. Spiegelman has now found that the zinc finger protein, in combination with a second protein produced in muscle cells, is the master switch for brown fat cells and will also convert skin cells into brown fat, even though this is not the process nature intended.

He has used this master switch to convert mouse skin cells to brown fat cells, which seem to work as expected when transplanted into normal mice. Now he is working on a second experiment, a crucial test for the possibility of therapy, to see what happens when brown fat cells are implanted into obese mice.

Asked if the mice were any thinner, Dr. Spiegelman said the results so far were encouraging. He declined to go further, saying journal editors would be unhappy if he gave away the findings before publication.

A similar procedure might be tried in people, he said, if the mouse experiments are promising. Further discoveries might produce the natural protein for turning on the zinc finger switch, and this protein might make a useful drug for converting skin cells into brown fat cells.

Dr. Enerback said Dr. Spiegelman had taken a "really important step" in elucidating the basic biology of brown fat cells. According to his calculations, Dr. Enerback said, inserting 50 to 100 grams of brown fat cells into a person would enable them to burn off more than 10 pounds of white fat tissue a year.

He said a cell therapy approach of this kind would allow a brown fat deposit of cells made from the patient's skin cells to be made larger or smaller according to need. Such a therapy would be used not by itself but along with lifestyle changes and other interventions.

Brown fat cells induce the body's white fat cells to break down their fat into fatty acids. These are released into the bloodstream and taken up by the brown fat cells. Brown fat cells contain large numbers of mitochondria, the chemical batteries of living cells.

The mitochondria (which originated long ago as bacteria enslaved in cells) usually generate a chemical form of energy. But in brown fat cells, this process is disrupted and the mitochondria produce heat instead.

Because the mitochondria contain iron, the cells adopt the brownish tinge that gives them their name.

[Mikey]

Holy crap.

Really. I mean, tinkering with the triggers of the genome. I am astounded.

[Aaron]

Hey man, I need my fat for the inevitable ice age!

[Tsukiyumi]

Hey man, I need my fat for the inevitable ice age!

I saw this on Nova the other day; very cool. It could help people like me, who can't do a lot of aerobic exercise.

[IanKennedy]

[Mikey]

Are those the brown fat cells, or have the Irish scientists finally reached the pinnacle of potato modification?

[Captain Seafort]

They're Adipose

[Mikey]

That has got to be the most obvious naming convention for an alien species I've ever heard.

[Sionnach Glic]

Yep.

They're also bizzarely adorable.