Peptide blasts fat cells in obese mice

The technique involves ablating the blood vessels that are laid down to supply white adipose tissue, the primary store for fat in the body, which in turn should lead to the destruction of the tissue. A similar approach has already been used in studies to treat tumours, but this is the first time that its use in treating obesity has been explored.

The researchers, from the MD Anderson Cancer Centre and Baylor College of Medicine in the US, identified a membrane protein called prohibitin that seems to be only found on the surface of cells in blood vessels that supply white adipose tissue. They then designed a peptide that binds to prohibitin and stimulates the cell to commit suicide, a process known as apoptosis.

The peptide was delivered by injection - every day for a month - to mice that were obese because they had been fed a high-calorie diet. By the end of the treatment period, white fat mass was reduced to the extent that normal body weight had been restored.

Renata Pasqualini, professor of medicine and cancer biology at MD Anderson, told DrugResearcher.com​ that prohibitin is not found on other tissues, including brown adipose tissue, so the effects of the therapy should be very localised.

"No adverse effects have been seen in mice, but the next step is to evaluate the properties of the drug in other species,"​ she added, noting that baboons are the next step towards clinical developmentm and a study should get going this summer.

And because the human version of prohibitin is very similar to that found in mice, it should be possible to develop similar fat-targetting drugs for obese patients.

Dr Pasqualini said that it is difficult to predict when human trials could take place, as US Food and Drug Administration (FDA) requirements are stringent for anti-obesity drugs as compared to anticancer drugs, for example, as it is considered that a drug for obesity has to be exceedingly safe.

The latest work bears interesting comparison with research carried out at Brigham and Women's Hospital in Boston, US, by a team headed by Maria Rupnick. This used several drugs designed to inhibit the creation of new blood vessels or angiogenesis in tests involving obese mice.

Interestingly, the results indicated that the mice lost a large amount of body weight, suggesting that inhibiting angiogenesis was in some way affecting the vasculature of existing as well as new blood vessels in adipose tissue. The nature of fat tissue is that it can grow and shrink very quickly, to either store or release fat reserves, and it is thought this may make its vasculature more malleable than other tissues in the body.

While Dr Pasqualini cautioned that no head-to-head studies of the two approaches have been conducted, she hypothesised that an ablative approach could be preferable as it is more selective to the target fat tissue.

In 1995, there were an estimated 200 million obese adults worldwide and another 18 million under-five children classified as overweight. As of 2000, the number of obese adults has increased to over 300 million. Contrary to conventional wisdom, the obesity epidemic is not restricted to industrialized societies; in developing countries, it is estimated that over 115 million people suffer from obesity-related problems.

Despite major progress in the understanding of the molecular mechanisms behind it, no safe and effective treatment has yet been found.

The ablation research is being funded by the US National Institutes of Health and philanthropic foundations, and to date no pharmaceutical company is involved in the research.