Stress, neuropeptide link may be key to fighting obesity, revolutionizing cosmetic surgery

National report - Investigators at Georgetown University Medical Center, Washington, say they used simple, nontoxic chemical injections to add and remove fat in targeted areas on the bodies of laboratory mice.

Researchers say the discovery, published online in Nature Medicine on July 1, could one day revolutionize human cosmetic and reconstructive plastic surgery, as well as treatment of obesity-associated diseases. The findings may also lead to better control of metabolic syndrome.

Chronic or prolonged stress is a key factor in the creation and maintenance of fat, according to the published paper. The signaling pathway - neuropeptide Y and its cellular receptor Y2 - plays a crucial role in this process.

Study methodology

Mice were regularly exposed to stresses such as standing in cold water or the presence of aggressive mice, which increased circulating levels of neuropeptide Y (NPY).

Only chronically stressed animals fed a high-fat diet developed abdominal obesity in two weeks, and within three months, metabolic syndrome-like condition.

Early studies found that "Stress-activated sympathetic nerves are releasing neuropeptide Y in blood vessels themselves, and that NPY attracts macrophages, which invade vessel walls," says Dr. Zukowska, who labels the process "neuroinflammation."

"We think that a similar process occurs in the fat as well," she says.

In the mice on the high-fat diet, investigators "noticed an invasion of the subcutaneous and visceral fat with macrophages, which is seen in human metabolic syndrome."

Release of NPY and activation of its receptor stimulated fat angiogenesis, macrophage infiltration and an increase in both the number of fat cells and their lipid content. The macrophages seemed to amplify this feedback loop, and the result was abdominal obesity and a metabolic syndrome-like condition.

'Melting' the fat

"We found that if we block the receptor, not only can we prevent the fat from developing, the same antagonist can be used to 'melt the fat'" in animals that have become obese, Dr. Zukowska says.

"It doesn't happen overnight, which is probably very good, but slowly, within two weeks, we can reduce the fat pockets by 50 percent in these animals," she says.

"Over the course of three months, there are reduced metabolic problems of central obesity, such as fatty liver, hypertension and glucose intolerance."

The role and function of the NPY-Y2 receptor pathway is very well conserved between mouse and man. Dr. Zukowska demonstrated a similar effect by injecting human liposuction fat into a nude mouse.

"Normally the injected fat gets absorbed within three months. But in the presence of neuropeptide Y, it not only survived, it revascularized, with vessels growing from the mouse."

Possible applications

Dr. Zukowska believes that local supplementation of NPY will be useful to either grow fat or maintain its survival when used in plastic surgery to reconstitute a breast after a mastectomy or in reconstructive facial surgery.