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                           JeffNEWS, June 1, 1995
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Obesity in Humans May Be Result of How Brain Receives `Stop Eating' Message
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Researchers at Jefferson Medical College have cloned and sequenced the 
mouse obesity gene in humans, and their findings indicate that both lean and 
obese individuals have the same genetic material. They suspect, however, 
that the difference that causes obesity lies in the way the brain receives 
its signal. Their findings were published in today's Journal of Clinical 
Investigation.

"While recent studies have revealed an abnormal gene in obese mice, our 
team has found no abnormalities in this gene. Rather, we found an increase 
in the production of a message protein that helps to regulate food 
consumption." explained Jose F. Caro, MD, chairman of Jefferson's department 
of medicine and senior author of the study. 

"The good news for 75 million Americans who are seriously overweight is 
that research efforts can now be redirected to investigate the possible 
abnormalities in the system that controls body weight. What this means is 
that it may be easier to activate a normal gene rather than to replace an 
abnormal one."

In the article, the Jefferson investigators report that both lean and 
obese humans have the same genetic material to secrete a protein - "satiety 
factor" - that is believed to send a "stop eating" message to the brain. The 
difference appears to be that obese individuals may be receiving the message 
incorrectly, and therefore they continue eating when in fact they should 
stop ingesting food. According to Dr. Caro, if the protein produced by the 
obesity gene proves to be a satiety factor, it should be possible to make 
adipose, or fat, tissue increase the production of the factor.

In lean humans, the obesity gene appears to cause fat cells to secrete a 
satiety factor (or appetite suppressant) that tells the brain how much fat 
storage is left. If fat storage increases, the obesity gene sends a message 
to the cell to produce more protein. If fat storage decreases, the satiety 
factor decreases and the brain activates appetite to avoid malnutrition. In 
this way, feeding is regulated to keep normal weight. When some steps of 
this delicate feedback loop system fail, the brain never learns that ample 
fat is in storage, which results in worsening of obesity.

Dr. Caro's team suggest that if the protein produced by the obesity gene 
is indeed a satiety factor - and this is yet to be proven - then the defect 
in human obesity lies outside of the gene itself. They speculate that:

* A brain receptor that is supposed to receive the protein signal may be 
  blocked or defective.

* The protein may degrade in transit and never reach its target.

* The protein may signal for the release of another, as yet unidentified 
  hormone, which may be defective.

"Clearly obesity research has entered the realm of molecular medicine, and 
we believe that a rational therapy will be found," said Dr. Caro. "Obesity 
truly is a disease, and is in fact a `complex disease,' along with 
hypertension, ischemic heart disease and diabetes. The term `complex 
disease' has been coined for conditions that arise from multifaceted 
interactions of environmental and genetic factors. In fact, it may be the 
most serious of the "complex diseases" since its presence significantly 
worsens the other three."

If you are interested in attending a summer seminar on obesity, call 1-
800-JEFF-NOW.

Obesity is defined as being 20 percent above the body weight determined by 
current charts.


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Information provided by:  Editor, JeffNEWS
                          (215) 955-6204
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