By genetically
engineering massively obese mice, an international team of scientists has
uncovered how the brain tells the body to burn calories and lose weight.
The finding
could lead to a better understanding of the processes linked to obesity
and help researchers develop new weight-loss drugs.
"The goal is
to understand the wiring behind diet control," senior researcher Bradford
Lowell, of Beth Israel Deaconess Medical Center, told United Press International.
No matter how
little or how much people eat, some remain obese while others stay lean,
Lowell said. Even identical twins can demonstrate remarkable differences.
One key biochemical
mechanism for shedding weight is an internal furnace that converts food
directly into body heat instead of stored fat, a complicated process called
"diet-induced thermogenesis," he said.
Scientists
long have assumed the nervous system maintains important links to this
intricate system, but until now there has been no direct evidence. Lowell
and researchers both in the United States and Italy focused their attention
on protein structures that dot the surfaces of cells. These proteins, known
as beta adrenergic receptors, latch onto and are activated by brain-released
biochemicals such as adrenaline and its cousin norepinephrine.
Both are neurotransmitters,
key components in the body's "fight or flight" system. They increase heart
rate, metabolism and blood flow to muscles.
Lowell and his
team knocked out the genes for all three known beta adrenergic receptors
in laboratory mice.
When the genetically
altered mice were fed standard rat chow, they became only mildly obese
after 20 weeks, and both normal and "beta-less" mice weighed about 25 grams
at about three months of age.
However, when
given a high-calorie, high-fat diet, the beta-less mice grew "massively
obese" over eight weeks, Lowell said, gaining 27 grams on average compared
to only six grams among normal mice. "I never expected an effect as big
as I saw in these mice," he noted. "That's all fat that they gained."
Both the beta-less
mice and their normal counterparts ate identical amounts of food. "The
beta-less group could not expend the extra calories," lead researcher Eric
Bachman, also of Beth Israel Deaconess, explained.
Future research
should pinpoint which tissues the receptors are activating, with prime
candidates the liver, kidneys, heart, muscles and even fatty tissue, physiologist
Abdul Dulloo, of the University of Fribourg in Switzerland, told UPI. This
should "lead to the development of safer and more efficacious drugs that
raise metabolic rate," he said.
Dulloo cautioned,
however, that mouse results do not necessarily carry over to humans, given
differences in genetic makeup and "problems in scaling from a 30-gram mouse
to a 75-kilogram human -- a 2,500-fold increase."
The findings
are published in the Aug. 2 issue of the journal Science.
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Copyright 2002 by United
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