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Scientists discover key to manipulating fat; Pathway also explains stress-induced weight gain
In what they call a "stunning research advance," investigators 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. The study's senior author is Zofia Zukowska, M.D., Ph.D., professor and chair of the Department of Physiology & Biophysics at Georgetown University Medical Center. The study, published online in Nature Medicine on July 1, 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. Sixty million Americans were estimated to be affected by metabolic syndrome in 2000, according to a study funded by the Centers for Disease Control in 2004.
n the paper, the Georgetown researchers describe a mechanism they found by which stress activates weight gain in mice, and they say this pathway − which they were able to manipulate − may explain why people who are chronically stressed gain more weight than they should based on the calories they consume. The researchers found that both a neurotransmitter (NPY) and the receptor (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 administration of Y2R blocker into the abdominal fat.
More immediately, the findings could provide some comfort to stressed individuals who blame themselves for a weight gain that seems outsized given the food they eat, said Lydia Kuo, a medical student who earned her Ph.D. in physiology due to work on the study. "This is the first study to show that stress has a direct effect on fat accumulation, body weight and metabolism," she said. "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."
And perhaps the most rapid clinical application of these results will be in both 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.
Roxanne Guy, MD, president of the American Society of Plastic Surgeons, of which Baker is a member, is also excited by the findings, although she agrees that more research is needed to find out how the animal findings translate in humans. "Providing a long lasting, natural wrinkle filler and a scientifically studied, non-surgical method for melting fat could revolutionize 'growing old gracefully,'" she said. "This discovery could also have positive implications for reconstructive plastic surgery procedures performed on the face and breasts."
As part of the study, 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. This finding makes sense if evolutionary advantage is considered, 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.
"The same mechanism may be happening in humans," she said. "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."
"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 Zukowska, "we are encouraged that these findings could improve human health."
In what they call a "stunning research advance," investigators 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. The study's senior author is Zofia Zukowska, M.D., Ph.D., professor and chair of the Department of Physiology & Biophysics at Georgetown University Medical Center. The study, published online in Nature Medicine on July 1, 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. Sixty million Americans were estimated to be affected by metabolic syndrome in 2000, according to a study funded by the Centers for Disease Control in 2004.
n the paper, the Georgetown researchers describe a mechanism they found by which stress activates weight gain in mice, and they say this pathway − which they were able to manipulate − may explain why people who are chronically stressed gain more weight than they should based on the calories they consume. The researchers found that both a neurotransmitter (NPY) and the receptor (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 administration of Y2R blocker into the abdominal fat.
More immediately, the findings could provide some comfort to stressed individuals who blame themselves for a weight gain that seems outsized given the food they eat, said Lydia Kuo, a medical student who earned her Ph.D. in physiology due to work on the study. "This is the first study to show that stress has a direct effect on fat accumulation, body weight and metabolism," she said. "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."
And perhaps the most rapid clinical application of these results will be in both 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.
Roxanne Guy, MD, president of the American Society of Plastic Surgeons, of which Baker is a member, is also excited by the findings, although she agrees that more research is needed to find out how the animal findings translate in humans. "Providing a long lasting, natural wrinkle filler and a scientifically studied, non-surgical method for melting fat could revolutionize 'growing old gracefully,'" she said. "This discovery could also have positive implications for reconstructive plastic surgery procedures performed on the face and breasts."
As part of the study, 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. This finding makes sense if evolutionary advantage is considered, 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.
"The same mechanism may be happening in humans," she said. "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."
"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 Zukowska, "we are encouraged that these findings could improve human health."
