Oregon Health & Science University scientist Michael Cowley, Ph.D., will present research findings about an appetite-reducing hormone found naturally in the body this week during the 2002 Society for Neuroscience meeting in Orlando, Fla. OHSU researchers collaborated with the Imperial College of Science, Technology and Medicine in London to study the impacts of the hormone secreted from fat tissue in the gut on certain neurons in the brain involved in weight regulation. Their results were published in the Aug. 8 edition of the journal Nature. Cowley's presentation of the findings will take place on Wednesday, November 6, at the annual neuroscience meeting.
Scientists found that peripheral hormone peptide YY (PYY 3-36) caused an approximate 35 percent drop in food intake when introduced to a bundle of neurons called the arcuate nucleus. This group of brain cells is located in the hypothalamus. Past research has shown that PYY 3-36 concentrations in the blood rise following a meal. This rise in blood concentrations leads researchers to believe that this hormone is one of the body's natural signaling systems used to communicate when a person has had enough to eat.
Identifying the arcuate nucleus was possible through the use of a method pioneered by OHSU researchers Roger Cone, Ph.D., Malcolm Low, M.D., Ph.D., and Michael Cowley, Ph.D. These 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.
"We're pleased to characterize another endogenous pathway that has the ability to impact food intake," said Cone, a senior scientist at the OHSU Vollum Institute. "However, scientists still have a long way to go before the development of a drug that can help fight severe obesity."
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 neuroscience at the OHSU Oregon National Primate Research Center. "Our next step in this research is to look at the effects of long-term PYY 3-36 treatment on animals, using obese rhesus macaque monkeys as a model."
Roger D. Cone, Ph.D., associate professor of cell and developmental biology in the OHSU School of Medicine, and a senior scientist in the Vollum Institute at OHSU
Michael A. Cowley, Ph.D., assistant scientist in 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