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First published online May 24, 2005
Journal of Experimental Biology 208, iv (2005)
Copyright © 2005 The Company of Biologists Limited
doi: 10.1242/jeb.01648
Outside JEB |
RATS THAT CAN'T RUN CAN'T HIDE FROM RISK FACTORS
University of Washington
crowther{at}u.washington.edu
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At a time when transgenic organisms are all the rage in biological research, it's nice to know that some hypotheses can still be tested with experimental animals created the old-fashioned way: through selective breeding. Since 1996, Steven Britton and Lauren Koch of the University of Michigan have used rats bred for high and low aerobic exercise capacity to address numerous questions about exercise performance, cardiac function and cardiovascular regulation. Their latest study of these rats - a collaboration with colleagues at the Norwegian University of Science and Technology, the Medical College of Ohio, and Williams College (Massachusetts) - probes the apparent link between aerobic capacity and cardiovascular and metabolic diseases.
Aerobic capacity, abbreviated
O2max, is an
animal's maximum rate of oxygen consumption per unit time. It is often
measured by having an animal run on a treadmill that gets progressively
steeper until the animal becomes exhausted. At the cellular level,
O2max reflects
the ability of the mitochondria to use oxygen for ATP production. Individuals
with a low O2max
typically have a lower-than-normal density of mitochondria in their muscle
cells, the chief oxygen consumers during intense exercise.
Beginning with a mixed population of rats, the researchers mated the best treadmill runners with each other and did likewise for the worst runners, testing the offspring's running ability and selecting the extreme individuals for the next round of mating. After 11 generations of this selective breeding, the population of high-capacity runners could run about 350% farther than the low-capacity runners during a progressive treadmill test. The team found that the low-capacity runners exhibited a variety of symptoms associated with an increased risk of cardiovascular and metabolic diseases. These included high blood pressure, impaired relaxation of blood vessels, insulin resistance, impaired cardiac pumping ability, and elevated triglyceride and free fatty acid levels in the blood. To add insult to injury, the low-capacity runners were also fatter than the high-capacity runners.
These data add new weight to previous suggestions that a low
O2max per
se can lead to the development of symptoms like those listed above. If
there is indeed a cause-and-effect relationship, it may well involve the
mitochondria; several transcription factors and enzymes essential for
mitochondrial function were 60-90% lower in the low-capacity runners' muscle
than in the high-capacity runners' muscle. However, the possible connections
between these proteins and cardiovascular variables such as blood pressure
remain open to speculation at present.
To what extent can exercise training protect individuals from the risks
associated with low
O2max? When the
team trained low-capacity runners on treadmills for six weeks, they noticed
that several measures of cardiac function improved along with
O2max. However,
they did not quantify the effects of training on the other above-mentioned
risk factors; presumably, the team will examine these in a subsequent report.
Aerobically impaired rats and humans will undoubtedly await these results with
interest.
References
Wisløff, U., Najjar, S. M., Ellingsen, Ø., Haram,
P. M., Swoap, S., Al-Share, Q., Fernström, M., Rezaei, K., Lee, S. J.,
Koch, L. G. and Britton, S. L. (2005). Cardiovascular risk
factors emerge after artificial selection for low aerobic capacity.
Science 307,418
-420.
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