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Fitness & Exercise for Senior Citizens
'Exercise pill' Switches on Gene Telling Cells to
Burn Fat
Even on high-fat diet normal mice were resistant to
weight gain
 April
30, 2007 – Imagine taking a drug that causes your body to start burning
fat as if you were taking part in vigorous exercise. It may not be ready
for humans but a scientist says he has achieved this amazing result with
mice. His hope is it will lead to prevent obesity and the health
consequences for so many senior citizens, such as heart disease, high
blood pressure and diabetes.
By giving ordinary adult mice a drug - a synthetic
designed to mimic fat - Salk Institute scientist Dr. Ronald M. Evans is
now able to chemically switch on PPAR-d, the master regulator that
controls the ability of cells to burn fat. Even when the mice are not
active, turning on the chemical switch activates the same fat-burning
process that occurs during exercise. The resulting shift in energy
balance (calories in, calories burned) makes the mice resistant to
weight gain on a high fat diet.
The hope, Dr. Evans told scientists attending
Experimental Biology 2007 in Washington, DC, is that such metabolic
trickery will lead to a new approach to new treatment and prevention of
human metabolic syndrome. Sometimes called syndrome X, this consists of
obesity and the often dire health consequences of obesity: high blood
pressure, high levels of fat in the blood, heart disease, and resistance
to insulin and diabetes.
Dr. Evan's Experimental Biology presentation on
April 30 is part of the scientific program of the American Society for
Biochemistry and Molecular Biology.
This chemical switch is not the first success Dr.
Evan's laboratory has had in being able to turn on the PPAR-d switch in
adipose or fat cells, activating local metabolism and increasing the
amount of calories burned.
As a Howard Hughes Medical Investigator at The Salk
Institute's Gene Expression Laboratory, Dr. Evans discovered the role of
the gene for PPAR-d, the master regulator of fat metabolism. By
permanently turning on this delta switch in mice through genetic
engineering, he was able to create a mouse with an innate resistance to
weight gain and twice the physical endurance of normal mice. Because
they were able to run an hour longer than a normal mouse, they were
dubbed "marathon mice."
Subsequent work in the Evans laboratory found that
activation of PPAR-d in these mice also suppresses the inflammatory
response associated with arthrosclerosis.
But the genetic metabolic engineering that created
the marathon mouse is permanent, turned on before birth. While a
dramatic proof of concept that metabolic engineering is a potentially
viable approach, it offers no help to an adult whose muscles are already
formed and who now would benefit greatly from having more active,
fat-burning muscles.
That is why the potential of chemical metabolic
engineering - possibly a one-a-day pill as opposed to permanent genetic
metabolic engineering - is so exciting, says Dr. Evans.
In today's society, too few people get an ideal
amount of exercise, some because of medical problems or excess weight
that makes exercise difficult. Having access to an "exercise pill" would
improve the quality of muscles, since muscles like to be exercised, and
increase the burning of energy or excess fat in the body. And that would
result in less fatty tissue, lower amounts of fat circulating in the
blood, lower blood glucose levels and less resistance to insulin,
lowering the risks of heart disease and diabetes.
The ability to chemically engineer changes in
metabolism also has given the researchers more insight into how the PPAR-d
switch works, says Dr. Evans. Genetically engineering changes in
metabolism in the marathon mice triggers both increased fat burning and
increased endurance.
Adult normal mice that receive the drug to switch
on PPAR-d show increased fat burning and resistance to weight gain, but
they do not show increased endurance. Dr. Evans says this suggests the
delta switch can operate in different modes, and the laboratory is in
the process of figuring out exactly how. He hopes his strategy will make
it possible.
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