Something for the FAT Conscious

By Maggie Fox
WASHINGTON, May 9 Reuters - A new approach being usedto fight cancer may also help fight fat, US researcherssaid today.
They said blocking a certain protein seemed toliterally vacuum fat off mice.
When fat mice were injected with the newfat-zapper'' every day for a month they all slimmeddown to normal weight with no visible side-effects, theresearchers reported in the June issue of NatureMedicine. But they stressed the experiment was still in the veryearly stages and it affected a function found invirtually all cells - meaning it had a high potentialfor serious side-effects. I am trying to un-hype this,’’ said Dr Wadih Arap ofthe M.D. Anderson Cancer Centre in Houston, who led theresearch.
In cancer, a new class of drugs called angiogenesisinhibitors starve tumors by cutting off their bloodsupply.
Arap and colleagues have turned this approach againstfat.
It makes sense, Arap argues - fat cells grow andproliferate quickly just as cancer cells do. Liketumours, they build themselves a scaffold of tiny bloodvessels called capillaries for sustenance.
Cancer drugs tackle different proteins involved inbuilding blood vessels. Arap’s team looked for a proteinthat might be found only in the blood vessels that feedfat cells.
They found one. Prohibitin is active on the surface offat-feeding blood vessels. They also found a monoclonalantibody - a synthetic immune system molecule - thatfinds and attaches to prohibitin alone.
If even a fraction of what we found in mice relatesto human biology, then we are cautiously optimistic thatthere may be a new way to think about reversingobesity,'' said Renata Pasqualini, Arap's researchpartner and wife. Arap's team made the monoclonal antibody lethal byattaching it to another protein fragment or peptide thatcauses apoptosis - a natural programmed cell suicide. Then they put normal mice on what they called acafeteria diet’’. It is high in calories,'' Arapsaid in a telephone interview. The mice started outweighing just under an ounce, 20 to 25 grams, but more than doubled their weight on thediet. Then they injected half the mice with the newfat-killing molecule. After daily injections for amonth, the fat mice lost, on average, 30 per cent oftheir body weight. The weight loss was also accompanied by a reversalof fatty liver and glucose intolerance,’’ Arap said,describing two common complications of obesity. Theyactually looked better. You could see them walk and soon.'' They also tested ageing mice, which tend to get fat.They responded just the same. They looked a littlethinner,’’ he said.
Arap said his team saw no side-effects. They didn'thave any signs of being ill,'' he said. All measureslook improved. If they had a side-effect we couldn’tdetect it.’’
Arap’s team did not measure how long their mice livedand they did not measure lean body mass to see if themice lost healthy muscle tissue too.
Next they plan to test baboons, which tend to put onweight much as humans do.
Arap noted that other research in which fat rodentshave miraculously lost weight had not translated tohumans. And prohibitin is found inside cells, whichmeans that accidentally disrupting it there could causesevere side-effects.
``I think it will be a while before we know whetherthis will be duplicated in humans,’’ he said.
Reuters ao