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Abdominal obesity may be reduced by Y2R inhibitor


Researchers at Georgetown University Medical Center have been able to use simple, non-toxic chemical injections to add and remove fat in targeted areas on the bodies of laboratory animals.
They say the discovery, published in Nature Medicine, could revolutionize human cosmetic and reconstructive plastic surgery and treatment of diseases associated with human obesity.

Investigators say these findings may also, over the long-term, lead to better control of metabolic syndrome, which is a collection of risk factors that increase a patient’s chances of developing heart disease, stroke, and diabetes.

In the paper, the Georgetown researchers describe a mechanism they found by which stress activates weight gain in mice, and they say this pathway may explain why people who are chronically stressed gain more weight than they should based on the calories they consume.

This pathway involves two players − a neurotransmitter ( neuropeptide Y, or NPY ) and the receptor ( neuropeptide Y2 receptor, or Y2R ) it activates in two types of cells in the fat tissue: endothelial cells lining blood vessels and fat cells themselves.

In order to add fat selectively to the mice they tested, researchers injected NPY into a specific area. The researchers found that both NPY and Y2R are activated during stress, leading to apple-shape obesity and metabolic syndrome. Both the weight gain and metabolic syndrome, however, were prevented by administration of Y2R blocker into the abdominal fat.

This is the first study to show that stress has a direct effect on fat accumulation, body weight and metabolism.

As part of the study, Zofia Zukowska and her team examined the effect of several forms of chronic stress that mice in the wilderness can encounter, such as exposure for an hour a day over a two-week period to standing in a puddle of cold water or to an aggressive alpha mouse, and they conducted the experiments in combination with a regular diet or with a high-fat, high-sugar diet. Stressed animals fed a normal diet did not gain weight, but stressed mice given a high-fat diet did. In fact, the researchers found these mice put on more weight than expected given the calories they were consuming.

“ They gained twice as much fat as would be expected, and it was all in their belly area, ” Kuo said. Stressed versus non-stressed animals ate the same amount of food, but the stressed animals processed it differently, she said, explaining, “ the novel finding here is that NPY works on fat tissue, not in the brain.”

“ The same mechanism may be happening in humans, ” Zukowska said. “ An accumulation of chronic stressors could be acting as an amplifier to a hypercaloric diet when protracted over time. Depression may also be acting as a stressor. ”

Not only were the stressed mice much fatter, they began to exhibit the metabolic and cardiovascular consequences of obesity, Lydia Kuo said. “ They had the glucose intolerance seen in diabetes, elevated blood pressure, inflammation in the blood vessels, and fat in their livers and muscles.”

Source: Georgetown University Medical Center, 2007

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