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Want to be slim? Cut your blood supply

Tim Radford, science editor
Monday May 10, 2004
The Guardian

Scientists have found a new way to make the obese slim again - by cutting off the blood supply to the layers of fat that are a health hazard for hundreds of millions of people.
The technique called "molecular liposuction" so far works only in mice. A team at the University of Houston, Texas, report in Nature Medicine today that weeks of treatment by an experimental drug restored the normal weight of mice that had doubled their size on a high-fat "cafeteria" diet.

"If even a fraction of what we found in mice relates to human biology, then we are cautiously optimistic that there may be a new way to think about reversing obesity," said Renata Pasqualini, of the University of Texas at Houston.

Obesity is now one of the biggest problems in world health. Almost one American in three is seriously overweight. One British male in four is clinically obese. Even in the developing world, obesity levels are rising rapidly. Obesity has been linked to adult-onset type 2 diabetes, cardiovascular hazards and increased risks of cancer.

Health authorities have urged people to eat less, choose a diet richer in fruit and vegetables and exercise more.

Cosmetic surgeons have promoted liposuction - the drastic removal of fat - and stomach surgery. Geneticists have been trying to make a hereditary connection - because some groups of people seem to be at greater risk of obesity - and research groups have been studying the hormonal cycles linked with eating in the search for appetite-suppressing pills.

But the Texas team tried an approach already being investigated as a cancer treatment. In theory, life-threatening tumours would halt and dwindle if you could cut off the blood supply to the cancerous tissue. But fat tissue, too, depends on a steady supply of oxygen and nutrients delivered in the blood.

These fat cells are abnormally greedy for oxygen, and a pound of fat contains a mile of blood vessels, according to one estimate. Blood vessels differ according to the "postal code addresses" they serve. So the Houston scientists, based at the university's M D Anderson cancer centre, searched for unique protein markers that would identify only those blood cells that served white adipose or fatty tissue.

They found one called prohibitin, already known to regulate cell survival and growth. They attached to it a synthetic drug already known from cancer trial to cause a cell to self-destruct.

Then they injected it into mice that had become grossly overweight on a high-fat, sugary diet. Within four weeks, the mice had reached their normal weight again. The fat had been reabsorbed and metabolised.

Other collaborators looked for evidence of toxic or unpleasant side effects - such as fat accumulation in the liver and blood - and found none. But further trials are needed.

"White adipose tissue is unique because it resembles a tumour in that it can rapidly expand.

"For such rapid expansion, there must be a very active production of blood vessels to deliver oxygen, and in fact every single fat cell is encased by capillaries," said Mikhail Kolonin, who led the research at Houston.

http://www.guardian.co.uk/uk_news/story/0,3604,1212998,00.html

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