June 30, 2000 GAINESVILLE, Fla.---Most of us have experienced eating and eating until suddenly we're so stuffed we can hardly waddle from the table to the couch.
Now for the first time, scientists at the University of Florida and the University of Texas have pinpointed the time it takes for the human brain to signal it's full and which areas of the brain are involved in eating. As it turns out, 10 minutes is generally all that separates nutritiously satisfied from excessively gorged.
That knowledge could be key in the diagnosis and treatment of obesity and associated conditions.
By mapping changes in blood flow and oxygenation using a technique called functional magnetic resonance imaging, termed fMRI, the researchers were able to record activity changes in the neurons to determine where in the brain, and more important, when the physiological reactions to food occur, the scientists report in the June 29 issue of Nature.
"The hypothalamus has been known for many years as being related to the regulation of eating, but this is the first study in humans able to directly demonstrate that it undergoes dynamic and physiologic changes as a result," said primary investigator Yijun Liu, an assistant professor in the UF College of Medicine's department of psychiatry.
"Most importantly, using a noninvasive technique, this study determined there was a connection between the changes that occur in the human brain after eating and the traditional biochemical indicators in the body, which are increases in the levels of glucose and insulin in the blood," said Liu, who also is affiliated with the Evelyn F. and William L. McKnight Brain Institute of the University of Florida.
The findings could help scientists further comprehend how the brain responds to eating and food. That has important implications in better understanding the brain mechanisms involved in the development of obesity and obesity-related diabetes, and for devising and testing medications to treat the disorders down the road.
Nearly a quarter of American adults are obese and the number is steadily growing. Obesity, an abnormally high proportion of body fat, boosts the risk of heart disease and death and contributes to at least half of the chronic diseases in Western society, according to the National Institutes for Health.
Liu conducted the experiment while at the University of Texas Health Science Center at San Antonio in conjunction with Dr. Peter T. Fox, Jia-Hong Gao and Ho-Ling Liu. It is an extension of prior research done by Yijun Liu, Fox and others, which found that the brain's response to food is significantly delayed and diminished in obese people compared with participants who were lean. The results demonstrated that the brain, specifically the hypothalamus, works differently in thin people than it does in those who are heavy. That difference could be caused by obesity, the researchers said.
As reported in the Nature article, 18 participants fasted for 12 hours, then underwent continuous brain scanning for 48 minutes. The fMRI scan records in a series of high-resolution images the brain's activity in response to internal and external stimuli such as eating or drinking.
Ten minutes after the scanning began, participants were given a water solution containing 75 grams of dextrose, a type of sugar, administered through an oral tube. Blood samples were obtained simultaneously for testing of plasma glucose and insulin levels. As a control, eight of the participants also underwent an fMRI scan on a separate day after ingesting an equivalent amount of distilled water.
Using a new method Liu developed called temporal clustering analysis, the researchers were able to map over time changes in the brain activity. Liu presented the new technique in April at the annual meeting of the International Society of Magnetic Resonance in Medicine.
After the glucose ingestion, two peaks in brain response were detected. One was about 90 seconds later, which Liu said was related to swallowing and other aspects of the eating process itself. The activity was found in the cerebellum and several other regions of the brain. It likely was related to taste, smell or other food ingestion processes, Liu said.
The more important and sustained peak began about 10 minutes after the ingestion and was the brain's signal that it was physically full, Liu said. The peak lasted about two minutes and corresponded directly with an increase in sugar and insulin levels in the blood. In addition, the scientists were able to track that the brain changes at the time of the second peak were mainly in the hypothalamus, likely showing it is linked to regulating blood glucose levels, he said.
Brain activity in the control group was more evenly distributed over time and did not show peaks after the glucose.
The fullness signal in humans was triggered in about half the time expected. Previous research based on studies in rats found it took 20 minutes for the satiety signal to kick in.
One of the limitations of the study is that scans were taken of only a single slice of the brain. Effects on the whole brain, which Liu intends to investigate, could be more complicated.
There were a number of novel concepts about the research, but Liu's temporal clustering analysis technique has the widest application, said Fox, co-researcher and director of the Research Imaging Center at the University of Texas.
"This provides the ability to look over relatively long periods of up to an hour for events occurring in the brain," Fox said. "This gives us a very powerful way of looking at eating, and enhances our ability to develop other interventions and techniques to treat obesity."
In the meantime, however, Fox said the studies results seem to bolster the long-standing adage: Don't gobble your food. Eating slowly may provide more time for the feeling of fullness to occur, especially in the obese, whose fullness signals are slower and weaker, he said.
Anthony Comuzzie, an expert studying the genetics of obesity at the Southwest Foundation for Biomedical Research, a non-profit scientific institution in San Antonio, said the study's findings are an exciting advance.
The work provides a unique set of new observable characteristics for the study of obesity, he said, "which should help us get closer to the fundamental regulation of food intake."
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