U.S. Department of Health and Human Services

Getting Rid of Body Fat by Targeting Its Blood Supply

Results of recent research suggest it may one day be possible to achieve weight loss by targeting cells in the blood vessels of body fat. In previous work with mice, the researchers used a molecule called “adipotide” that binds only to blood vessels in white adipose tissue, which accounts for the great majority of fat in the body. The molecule triggers cell death specifically in the cells to which it binds. Although the mice given adipotide lost a great deal of weight, and seemed to suffer no obvious ill effects from the treatment, numerous previous weight loss methods that seemed promising in mice have failed to prove effective in humans. In the new research, therefore, scientists tested the approach in obese monkeys— an animal model that more closely mimics human obesity. Just as with humans, some monkeys become overweight or obese when given an abundant supply of whatever food they want to eat, while others do not. Also, as with humans, obesity in monkeys can lead to insulin resistance, type 2 diabetes, and other metabolic and cardiovascular problems. The scientists injected obese monkeys with doses of adipotide or placebo daily for 4 weeks, and then followed the animals for an additional 4 weeks. The monkeys receiving adipotide began to lose a significant amount of weight within the first week of treatment, and continued to lose weight for 3 weeks after treatment ended, losing a total of about 15 percent of their body weight in 7 weeks. Tests of body composition revealed that almost all of the weight lost was body fat, although mild dehydration did also occur. (In a separate experiment, the researchers showed that lean monkeys treated with adipotide did not lose weight, indicating that the drug works selectively on fat tissue.) The obese animals receiving adipotide ate less than their counterparts, although they seemed to continue to like their food. In other respects, their behavior was normal, during and after treatment. Adipotide-treated monkeys produced more urine than did control animals, and had significant but not serious increases in urine glucose and protein levels that reverted to normal after treatment. Notably, adipotide treatment also improved insulin sensitivity. Of some concern, the treatment also led to an elevation of serum creatinine, a sign of kidney damage. The elevated creatinine levels seen in the adipotide-treated monkeys fell during recovery, but remained slightly higher than in control animals. Direct examination of the kidneys revealed signs of slight damage which appeared to be reversible, but which suggests a possible side effect to watch for in potential future human trials. These results validate the general approach of reducing body fat by attacking its blood supply. Future research will determine whether adipotide or a similar agent would be safe and effective for weight loss in humans.
Barnhard KF, Christianson DR, Hanley PW, et al. A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys. Sci Transl Med 3: 108rall2, 2011.