Scientists Find Way to Block Weight Gain in Stressed People

In the quest for a perfect body, what if humans were able to lose a little weight here, while gaining a little weight there?

Scientists from Georgetown University Medical Center have found that blocking the pathway that leads stressed people to gain weight is the key to manipulating fat — at least in laboratory animals.

The findings, published online in Nature Medicine on Sunday, explain why people who are chronically stressed often develop "metabolic syndrome," a condition which causes individuals to gain more weight than they should based on the calories they consume.

Sixty million Americans were estimated to be affected by metabolic syndrome in 2000, according to a study funded by the Centers for Disease Control and Prevention in 2004.

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

The researchers found that both NPY and Y2R are activated during stress, leading to apple-shape obesity and metabolic syndrome.

With this understanding, researchers were able to add fat selectively to the mice by injecting NPY into a specific area. They were also able to block weight gain and metabolic syndrome by injecting the mice with Y2R blocker into the abdominal fat.

"We couldn’t believe such fat remodeling 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," said the study’s senior author, Zofia Zukowska, M.D., Ph.D., professor and chairman of the Department of Physiology & Biophysics at Georgetown University Medical Center, in a news release.

For the study, stressed animals fed a normal diet did not gain weight, but stressed mice given a high-fat diet did. 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," said Lydia Kuo, a medical student who earned her Ph.D. in physiology due to work on the study, also in a news release.

Stressed versus non-stressed animals ate the same amount of food, but the stressed animals processed it differently, she said, adding, "the novel finding here is that NPY works on fat tissue, not in the brain."

"We are hopeful that these findings might eventually lead to control of metabolic syndrome, which is a huge health issue for many Americans," Zukowska said. "Decreasing fat in the abdomen of the mice we studied reduced the fat in their liver and skeletal muscles, and 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."

The fat is most likely stored to give the stressed mice an evolutionary advantage, Zukowska said.

"If you can store fat for times of hardship, you have a fat reserve that can be turned into energy for the next fight," she said. "The same mechanism may be happening in humans. An accumulation of chronic stressors, like disagreements with your boss, taking care of a chronically ill child, or repeated traffic road rages, could be acting as an amplifier to a hypercaloric diet when protracted over time. Depression may also be acting as a stressor."

The research could lead to clinical uses in cosmetic and reconstructive plastic surgery, said co-author Stephen Baker, M.D., D.D.S, associate professor of plastic surgery at Georgetown University Hospital. The ability to add fat as a graft would be useful for facial rejuvenation, breast surgery, buttock and lip enhancement, and facial reconstruction, he said, and using injections like those tested in this study could make fat grafts predictable, inexpensive, biocompatible and permanent, he said.

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

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