By destroying the blood vessels that feed fat deposits, researchers at the University of Texas M.D. Anderson Cancer Center (Houston, TX) have induced rapid weight loss in obese mice. This work may one day lead to a treatment for obesity in humans.

With current estimates indicating that 65% of Americans are overweight and 30% are obese, these conditions have become a widespread and serious threat to public health. Indeed, overweight and obesity have been linked with an increased risk of a number of serious maladies, including diabetes, certain types of cancer, and cardiovascular disease, as well as with an overall reduction in life span.

Fat deposits are highly vascularized, with each adipocyte in contact with multiple capillaries. Armed with that knowledge, a team led by Renata Pasqualini and Wadih Arap developed a molecular therapy that destroys these blood vessels, causing fat cells to be resorbed and metabolized, resulting in drastic weight loss in mice.

The research team used an in vivo phage display technique to screen for a compound that would selectively target blood vessels in white fat. They then attached this sequence (referred to as CKGGRAKDC) to a synthetic peptide chain known to induce apoptosis in tumor blood vessels, to form a complex designated CKGGRAKDC-GG-D(KLAKAK)2. Mice that had become obese after feeding them with a high-calorie diet and were not genetically altered, lost ∼30% of their body weight in four weeks after receiving subcutaneous doses of the complex (Nature Medicine, June).

Although an increase in metabolism accompanied this weight loss, there was no association with increased physical activity or a reduction in food intake, when adjusted for body weight. In addition, the research team saw no side effects from this treatment.

The researchers determined that CCGGRAKDC homes in on the membrane protein prohibitin, which is also expressed in human white-fat vasculature, suggesting that CKGGRAKDC-GG-D(KLAKAK)2 may be an effective treatment for obesity in people. Pasqualini tells Lab Animal that her team is now preparing to test the compound for safety and efficacy in other species, including baboons, which tend to become obese in captivity.