Portland, Ore.
Finding helps explain weight control mechanism in the brain
Researchers at Oregon Health & Science University are part of an international research team that has located a compound found naturally in the body with the ability to limit food intake in both mice and humans. The compound, called peripheral hormone peptide YY (PYY), is typically released from the body's gastrointestinal tract in proportion to caloric intake. Some believe PYY may be one of the body's natural signals to the brain telling a person they are full and can stop eating. By introducing PYY into the bloodstreams of both humans and mice through infusions, researchers noted a temporary, however measurable drop in appetite and food ingestion. Scientists at the OHSU Vollum Institute and the OHSU Oregon National Primate Research Center collaborated with researchers at the Imperial College of Science, Technology and Medicine in London. Their findings are printed in the Aug. 8 edition of the journal Nature.
"This work is another piece in the puzzle that adds to the understanding of how hunger and satiety are controlled," said Roger Cone, Ph.D., a senior scientist at the OHSU Vollum Institute. "We're pleased to characterize another endogenous pathway that has the ability to impact food intake. However, scientists still have a long way to go before the development of a drug that can help the thousands of Americans fighting obesity problems. While PYY has the ability to curb a person's appetite, it would not make a suitable weight loss drug due to its potential effect on other important systems on the body and due to the fact that it does not have good drug-like properties."
An important aspect of the research was having the ability to pinpoint certain neurons in the brain and determine their response to PYY. This was possible through the use of a method pioneered by OHSU researchers Cone, Malcolm Low, M.D., Ph.D., and Michael Cowley, Ph.D. The three scientists developed a way by which key neurons give off a green fluorescence when viewed under a microscope. This allowed them to identify and record the activity of cells involved in the regulation of body weight called pro-opiomelanocortin (POMC) neurons when exposed to PYY and other substances.
After OHSU scientists examined the reaction of POMC neurons to PYY in mice, researchers in London studied the response in humans. A total of 12 healthy, non-obese volunteers received intravenous PYY or saline infusions for 90 minutes in a double-blind, placebo-controlled study. Two hours following the infusions, scientists measured caloric intake during a free-choice buffet meal. For those participants who received PYY infusions, there was a significant affect on food intake. This group reported that they felt less hungry and ate approximately one-third less calories than the control group receiving saline infusions. The PYY group's temporary reduction in appetite lasted approximately 12 hours. After that, the PYY group saw their appetites return to normal levels.
"Not only did the PYY group experience a drop in appetite, they did not have increased appetite later, and did not 'make up' for the food they missed," said Cowley, previously a scientist in the Cone lab, now an assistant scientist in the Division of Neuroscience at the OHSU Oregon National Primate Research Center.
The Cone lab has been studying POMC neurons for years. The cells are part of a brain circuit identified by the Cone laboratory as an important component of the adipostat. The adipostat is a brain mechanism that continually adjusts food intake and energy expenditure to maintain constant levels of fat.
"The adipostat acts like a fat thermostat in the body," said Cone "For those who have trouble losing weight through dieting, this is the brain mechanism most likely behind it. When a person goes on a diet, the adipostat thinks the person is starving so it takes steps to make the body work more efficiently by reducing metabolism and energy expenditure to conserve resources. This is why weight loss can be such a challenge. Through research like this we're not only interested in locating compounds that reduce appetite, we're also looking for ways to control the adipostat so people can lose weight and keep it off.
Particulars:
Roger D. Cone, Ph.D., assistant professor of cell and developmental biology in the OHSU School of Medicine, and a senior scientist in the Vollum Institute
Michael A. Cowley, Ph.D., assistant scientist in the Division of Neuroscience at the OHSU Oregon National Primate Research Center
Malcolm J. Low, M.D., Ph.D., professor of behavioral neuroscience in the OHSU School of Medicine, and a scientist in the Vollum Institute
"This work is another piece in the puzzle that adds to the understanding of how hunger and satiety are controlled," said Roger Cone, Ph.D., a senior scientist at the OHSU Vollum Institute. "We're pleased to characterize another endogenous pathway that has the ability to impact food intake. However, scientists still have a long way to go before the development of a drug that can help the thousands of Americans fighting obesity problems. While PYY has the ability to curb a person's appetite, it would not make a suitable weight loss drug due to its potential effect on other important systems on the body and due to the fact that it does not have good drug-like properties."
An important aspect of the research was having the ability to pinpoint certain neurons in the brain and determine their response to PYY. This was possible through the use of a method pioneered by OHSU researchers Cone, Malcolm Low, M.D., Ph.D., and Michael Cowley, Ph.D. The three scientists developed a way by which key neurons give off a green fluorescence when viewed under a microscope. This allowed them to identify and record the activity of cells involved in the regulation of body weight called pro-opiomelanocortin (POMC) neurons when exposed to PYY and other substances.
After OHSU scientists examined the reaction of POMC neurons to PYY in mice, researchers in London studied the response in humans. A total of 12 healthy, non-obese volunteers received intravenous PYY or saline infusions for 90 minutes in a double-blind, placebo-controlled study. Two hours following the infusions, scientists measured caloric intake during a free-choice buffet meal. For those participants who received PYY infusions, there was a significant affect on food intake. This group reported that they felt less hungry and ate approximately one-third less calories than the control group receiving saline infusions. The PYY group's temporary reduction in appetite lasted approximately 12 hours. After that, the PYY group saw their appetites return to normal levels.
"Not only did the PYY group experience a drop in appetite, they did not have increased appetite later, and did not 'make up' for the food they missed," said Cowley, previously a scientist in the Cone lab, now an assistant scientist in the Division of Neuroscience at the OHSU Oregon National Primate Research Center.
The Cone lab has been studying POMC neurons for years. The cells are part of a brain circuit identified by the Cone laboratory as an important component of the adipostat. The adipostat is a brain mechanism that continually adjusts food intake and energy expenditure to maintain constant levels of fat.
"The adipostat acts like a fat thermostat in the body," said Cone "For those who have trouble losing weight through dieting, this is the brain mechanism most likely behind it. When a person goes on a diet, the adipostat thinks the person is starving so it takes steps to make the body work more efficiently by reducing metabolism and energy expenditure to conserve resources. This is why weight loss can be such a challenge. Through research like this we're not only interested in locating compounds that reduce appetite, we're also looking for ways to control the adipostat so people can lose weight and keep it off.
Particulars:
Roger D. Cone, Ph.D., assistant professor of cell and developmental biology in the OHSU School of Medicine, and a senior scientist in the Vollum Institute
Michael A. Cowley, Ph.D., assistant scientist in the Division of Neuroscience at the OHSU Oregon National Primate Research Center
Malcolm J. Low, M.D., Ph.D., professor of behavioral neuroscience in the OHSU School of Medicine, and a scientist in the Vollum Institute
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