US Scientists have discovered how stress activates weight gain in mice and have also found a way to add and remove fat in targeted areas of the bodies of laboratory animals using simple, non-toxic chemical injections.

The research is published in the online edition of Nature Medicine.

The findings have been described as "stunning" and could revolutionize treatments for weight loss, obesity, cosmetic and reconstructive surgery in humans.

Researchers at Georgetown University Medical Center, Washington DC, hope their discoveries will eventually lead to better control of what has been termed "metabolic syndrome", a group of risk factors that together increase a person's chance of getting heart disease, diabetes and stroke.

According to the Centers for Disease Control and Prevention (CDC), estimates made in the year 2000 suggest some 60 Million Americans are affected by metabolic syndrome. Stress causes some people to lose weight and others to gain it. Scientists have suspected a link between stress and obesity but until now have not been able to pin it down.

The Georgetown researchers found a mechanism based on neurotransmitters that may explain why chronically stressed people put on more weight than would be expected from the calories they consume.

Neurotransmitters are chemicals used by a variety of neurons in the body to transmit signals to each other. For instance, acetylcholine regulates muscle movement, serotonin is involved in emotion regulation, temperature control and memory.

In this case, the researchers manipulated a neurotransmitter (neuropeptide Y or NPY for short) and the receptor (neuropeptide Y2 receptor or YR2 for short) that it activates. NPY and YR2 work in two types of cell in fat tissue: endothelial cells that line blood vessels and fat cells.

They found that stressors such as exposure to cold or aggression leads to the relase of NPY from sympathetic nerves, which is taken up by Y2R which in turn causes the release of more NPY. This positive feedback effect is what leads to the growth of abdominal fat, apple-shaped obesity and metabolic syndrome they said.

The researchers were able to add fat selectively to areas of the body in mice by injecting the sites with NPY.

And apple-shaped obesity (where weight gain is mainly around the middle) and metabolic syndrome were prevented by injecting Y2R blocker in the abdominal fat. The Y2R blockers stopped the uptake of NPY and broke the positive feedback cycle that was leading to the production of even more NPY.

The study's senior author, who is professor and chair of the Department of Physiology and Biophysics at Georgetown University Medical Center, Dr Zofia Zukowska said:

"We couldn't believe that such fat remodelling was possible, but the numerous different experiments conducted over four years demonstrated that it is, at least in mice; recent pilot data also suggest that a similar mechanism exist in monkeys as well."

"We are hopeful that these findings might eventually lead to control of metabolic syndrome, which is a huge health issue for many Americans," she added.

Dr Zukowska also said that increasing fat in the abdomen of the mice reduced the fat in their liver and skeletal muscle and it:

"Also helped to control insulin resistance, glucose intolerance, blood pressure and inflammation. Blocking Y2R might work the same way in humans, but much study will be needed to prove that."

In the meantime, this news may bring comfort to those stressed people who blame themselves for putting on far more weight than would seem reasonable for the amount of food they consume said the lead author, Dr Lydia Kuo, whose PhD was based on this work.

"In humans, this kind of stress-mediated fat gain may have nothing to do with the brain, and is actually just a physiological response of their fat tissue," said Dr Kuo.

Zukowska and colleagues tested the mice with stressors that mice would encounter in the wild such as cold exposure for an hour a day for two weeks to standing in a puddle of cold water or being in the company of an aggressive alpha mouse. They did the experiments in conjuction with feeding the mice a regular diet, a high fat and a high sugar diet.

Stressed animals on a normal diet did not gain weight, but stressed mice on a high-fat diet did. In fact, they found the mice on the high-fat diet actually gained more weight than would be expected from the calories they consumed, and it was all in the belly area, hence the link to apple shape.

The researchers concluded that NPY works on fat tissue, not the brain, and that the stressed animals processed their food differently to non-stressed animals.

Zukowska said this made sense when you think of the evolutionary advantage such a mechanism confers:

"If you can store fat for times of hardship, you have a fat reserve that can be turned into energy for the next fight."

It could be a similar pattern for humans. The stressor could be having a disagreement with your boss, looking after a sick child, or repeated incidents of road rage. These could amplify the hypercaloric effect on one's diet over time. Depression could be another stressor, she said.

The stressed mice, apart from gaining weight, also started to show the metabolic and cardiovascular results of being obese. Glucose intolerance went up, and so did blood pressure. Their blood vessels became inflamed and the fat content in their liver and muscles increased.

Another of the researchers, Dr Stephen Baker, associate professor of plastic surgery at Georgetown University Hospital, said that perhaps the most rapid application to emerge from these findings will be in the areas of cosmetic and reconstructive plastic surgery.

Using injections like those tested in this research could make fat grafts predictable, inexpensive, biocompatible and permanent, he said. This would be useful for facial rejuvenation, breast surgery, buttock and lip enhancement, and facial reconstruction, he added.

Also, referring to the study's finding that blocking Y2R resulted in localized reductions of adipose (fat tissue), Dr Baker said:

"This is the first well-described mechanism found that can effectively eliminate fat without using surgery. A safe, effective, non-surgical means to eliminate undesirable body fat would be of great benefit to our patients."

President of the American Society of Plastic Surgeons, Dr Roxanne Guy, said she was excited by the study but said, like the research team, a lot more research is needed to find out how these mechanisms work in humans:

"Providing a long lasting, natural wrinkle filler and a scientifically studied, non-surgical method for melting fat could revolutionize growing old gracefully."

"This discovery could also have positive implications for reconstructive plastic surgery procedures performed on the face and breasts, she added.

"Although we don't expect that, in the future, a person will be able to eat everything he or she wants, chase it down with a Y2R blocking agent, and end up looking like a movie star," said Dr Zukowska, "we are encouraged that these findings could improve human health."

"Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome."
Lydia E Kuo, Joanna B Kitlinska, Jason U Tilan, Lijun Li, Stephen B Baker, Michael D Johnson, Edward W Lee, Mary Susan Burnett, Stanley T Fricke, Richard Kvetnansky, Herbert Herzog and Zofia Zukowska.
Nature Medicine Published online: 01 July 2007.
doi:10.1038/nm1611

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Written by: Catharine Paddock
Writer: Medical News Today