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NIH Research Matters

July 9, 2007

Stress, Obesity Link Found

Some people quickly gain weight when they're stressed. A new study has uncovered a molecular connection between stress and weight gain. The discovery may lead to ways of helping people who are chronically stressed control their weight.

Picture of a mouse standing on a block of Swiss cheese.

Dr. Zofia Zukowska of Georgetown University Medical Center leads a team of researchers that previously showed a molecule called neuropeptide Y (NPY) is involved in angiogenesis, the growth of the blood vessels necessary to support new tissue growth. NPY is released from certain nerve cells during stress. Other research had shown that NPY and its receptors seem to play a role in appetite and obesity. Putting these results together, the researchers thought that NPY might be involved in new fat growth during stressful situations.

Funded in part by NIH's National Heart, Lung and Blood Institute (NHLBI) and National Institute of Dental and Craniofacial Research (NIDCR), the researchers tested the effects of chronic stress on fat growth in mice. They compared the effects of stress when the mice were fed a normal diet and one high in fat and sugar to reflect the comfort foods many people eat when they're stressed.

As they described online in the July 1, 2007, issue of Nature Medicine, the researchers found that making the mice stand in cold water or exposing them to an aggressive mouse for 10 minutes a day led to the release of NPY from nerves. For the mice eating the normal diet, stress had little effect on body fat. For those mice eating the high fat and sugar diet, however, stress led to a significant increase in belly fat over a 2-week period.

In the presence of the high fat and sugar diet, the researchers found, abdominal fat produced more NPY along with its receptor, NPY2R. This stimulated angiogenesis in fat tissue and the proliferation of fat cells, resulting in more belly fat. Eventually, after 3 months of stress and a high fat and sugar diet, the mice developed a metabolic syndrome-like condition. Metabolic syndrome in people is linked to abdominal obesity and increases your chance for heart disease, diabetes and other health problems.

The researchers then tested whether they could use NPY to manipulate fat levels. They put a pellet under the animals' skin that releases NPY over a period of 14 days. The pellet increased the amount of fat tissue in both genetically obese and lean mice by 50%. By contrast, injections with a molecule that blocks NPY2R decreased the amount of fat tissue in both obese and lean mice by 50%. The NPY2R-blocking molecule, the researchers found, decreased the number of blood vessels and fat cells in abdominal fat pads. NPY, then, acting through NPY2R, stimulates angiogenesis and fat tissue growth.

The researchers showed that NPY and its receptor also play a role in the growth of human fat cells. Other studies have found genetic evidence linking NPY and NPY2R to the regulation of obesity in people. Zukowska said, "We are hopeful that these findings might eventually lead to the control of metabolic syndrome, which is a huge health issue for many Americans."

—by Harrison Wein, Ph.D.

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Editor: Harrison Wein, Ph.D.
Assistant Editors: Vicki Contie, Carol Torgan, Ph.D.

NIH Research Matters is a weekly update of NIH research highlights from the Office of Communications and Public Liaison, Office of the Director, National Institutes of Health.

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This page last reviewed on August 3, 2012

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