"Cutting blood supply to kill off fat"

[gotbeer]

Week of May 29, 2004; Vol. 165, No. 22 , p. 350

Cutting blood supply to kill off fat

John Travis, Science News

http://www.sciencenews.org/articles/20040529/note15.asp

In a strategy dubbed molecular liposuction, researchers have created a drug that homes in on and destroys the blood vessels that sustain fat cells. Severely obese mice treated with the compound quickly shed fat until they reached normal weights, according to a report in the June Nature Medicine.

The new work follows up on similar findings reported in 2002. Then, Maria Rupnick of Brigham and Women's Hospital in Boston found that drugs designed to starve tumors by thwarting new blood vessel formation, or angiogenesis, also cause dramatic weight loss in obese mice. The drugs apparently have this effect because growing fat is particularly dependent on new blood vessels (SN: 8/3/02, p. 67: http://www.sciencenews.org/articles/20020803/fob1.asp).

Concerned that typical angiogenesis inhibitors might disrupt needed blood supplies elsewhere in the body, Wadih Arap of the University of Texas M.D. Anderson Cancer Center in Houston and his colleagues devised a way to selectively destroy the vascular system in fat. After identifying a small protein that travels specifically to blood vessels servicing fat tissue, the researchers affixed a cell-killing drug to the protein. In a matter of weeks, obese mice receiving the treatment had lost most of their excess fat.

References:

Kolonin, M.G. . . . and W. Arap. In press. Reversal of obesity by targeted ablation of adipose tissue. Nature Medicine. Abstract available at http://dx.doi.org/10.1038/nm1048.

Further Readings:

Travis, J. 2002. Fat chance: Cancer drugs may also thwart obesity. Science News 162(Aug. 3):67. Available at http://www.sciencenews.org/articles/20020803/fob1.asp.

Sources:

Wadih Arap
University of Texas
M.D. Anderson Cancer Center
Houston, TX 77030

From Science News, Vol. 165, No. 22, May 29, 2004, p. 350.

[gotbeer]

Nature Medicine 10, 625 - 632 (2004)

Published online: 09 May 2004 | doi:10.1038/nm1048

Reversal of obesity by targeted ablation of adipose tissue

Mikhail G Kolonin1, Pradip K Saha2, Lawrence Chan2, Renata Pasqualini1, 3 & Wadih Arap1, 3

1 The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.

2 Departments of Medicine and Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.

3 These authors contributed equally to this work.

Correspondence should be addressed to Renata Pasqualini rpasqual~mdanderson.org or Wadih Arap warap~mdanderson.org

http://www.nature.com/cgi-taf/DynaPage.taf?file=/nm/journal/v10/n6/abs/nm1048.html

Obesity is an increasingly prevalent human condition in developed societies. Despite major progress in the understanding of the molecular mechanisms leading to obesity, no safe and effective treatment has yet been found. Here, we report an antiobesity therapy based on targeted induction of apoptosis in the vasculature of adipose tissue. We used in vivo phage display to isolate a peptide motif (sequence CKGGRAKDC) that homes to white fat vasculature. We show that the CKGGRAKDC peptide associates with prohibitin, a multifunctional membrane protein, and establish prohibitin as a vascular marker of adipose tissue. Targeting a proapoptotic peptide to prohibitin in the adipose vasculature caused ablation of white fat. Resorption of established white adipose tissue and normalization of metabolism resulted in rapid obesity reversal without detectable adverse effects. Because prohibitin is also expressed in blood vessels of human white fat, this work may lead to the development of targeted drugs for treatment of obese patients.

[Dodger]

What seems to be lacking is the understanding by these researchers that obesity is a symptom, not a disease. It’s the excess insulin in the body that causes the fat storage and the heart problems. Creating drugs that get rid of the fat will result in thinner unhealthy people. These people will think they are healthier because of their weight, but they will still be eating lots of carbs and producing lots in insulin.



The only reasonable use for such drugs would be to treat those people who have a metabolic disorder that causes excess fat storage.