Experimental Drug Induces Weight Loss and Improved Insulin Resistance in Obese Monkeys

An experimental drug that destroys the blood vessels within white fat (adipose) tissue reduced the body weight of obese rhesus monkeys while improving their insulin resistance without causing major adverse side effects.

A population of rhesus monkeys that were obese due to overeating and lack of exercise was used to test the effects of adipotide (the ligand-directed peptidomimetic CKGGRAKDC-GG-D(KLAKLAK)2), which had been shown previously to reduce the body weight of obese mice by more than 30%.

Investigators at the University of Texas MD Anderson Cancer Center (Houston, USA) designed adipotide to bind to two receptors, ANXA2 and prohibitin, that are specific to blood vessels supplying white adipose tissue. They reported in the November 9, 2011, issue of the journal Science Translational Medicine that treatment with adipotide induced targeted apoptosis within blood vessels of white adipose tissue and resulted in rapid weight loss and improved insulin resistance. After four weeks of treatment, the obese monkeys lost on average 11% of their body weight. Lean monkeys in the control group did not lose weight, indicating that the drug’s effect may be selective for obese subjects.

Magnetic resonance imaging and dual-energy X-ray absorptiometry confirmed a 27% reduction in white adipose tissue in the treated monkeys while fat levels increased slightly in the control group.

“Most drugs against obesity fail in transition between rodents and primates,” said senior author Dr. Renata Pasqualini, professor of medicine and experimental diagnostic imaging at the MD Anderson Cancer Center. “All rodent models of obesity are faulty because their metabolism and central nervous system control of appetite and satiety are very different from primates, including humans. We are greatly encouraged to see substantial weight loss in a primate model of obesity that closely matches the human condition. Development of this compound for human use would provide a nonsurgical way to actually reduce accumulated white fat, in contrast to current weight-loss drugs that attempt to control appetite or prevent absorption of dietary fat.”

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