Making Better Muscles

Long-distance runners tend to be lean. They are at lower risk for diabetes than sedentary people. And their leg muscles can work for long periods without tiring.

Now a team of scientists at the Salk Institute in La Jolla, Calif., has shed light on why these three attributes of endurance training occur together. The research also suggests it may be possible both to increase athletic performance and to lose weight by activating a single protein in muscle.

Skeletal muscle comes in two forms. Type I contracts slowly, is full of the cellular power plants known as mitochondria, and it can be active for long periods without becoming exhausted. Marathoners have lots of it.

In contrast, Type II contracts quickly, does not require oxygen to make its fuel and tires rapidly. It is what makes up weight lifters' bulging biceps.

The balance between the two types changes with training; the switch is controlled in part by the activity of a receptor on muscle cells called PPAR-Delta.

Yong-Xu Wang, Ronald M. Evans and colleagues genetically engineered mice to have unusually active PPAR-Delta receptors. Compared with normal mice, they had twice as much Type I muscle, and more than twice as many mitochondria, in their legs. On treadmills, they could exercise an hour longer and go nearly twice as far as the others.

Fed high-fat diets, the mice with boosted PPAR-Delta activity gained only a third as much weight as normal animals. They also had better glucose tolerance -- a sign of resistance to diabetes.

Wang and Evans also found that if they fed normal mice a substance that stimulated the PPAR-Delta receptors, the animals grew Type I muscle, gained less weight and had better glucose tolerance.

In a finding likely to get attention in the worlds of both sport and medicine, the Salk scientists note that "activation of muscle PPAR-Delta essentially recapitulates the effects of exercise training, even in the absence of training itself."

The research was published in the biology section of the online journal Public Library of Science, available at www.plosbiology.org.

-- David Brown

Darwin's Finches, Continued

Every high school biology student has heard the tale of Darwin's finches. During his 1835 trip to the Galapagos Islands, Charles Darwin became obsessed with the immense variety of beak shapes adorning the islands' distinct populations of finches -- each one perfectly adapted to the kind of food consumed by that kind of finch.

Those adaptations became Darwin's prime example of how evolution worked and how, over time, natural selection could generate the world's great diversity of species. But he never had a clue about how, on the genetic and hormonal levels, those beaks actually grew into their respective shapes during fetal development.

Now scientists have finally cracked that egg.

Clifford J. Tabin and colleagues at Harvard Medical School examined the role of a gene called BMP4, versions of which have been found in many animal species. The gene allows cells to make a hormone called bone morphogenetic factor 4.

Scientists already knew that the hormone plays an important role in the development of bones. Tabin's group went further by using sophisticated imaging techniques to see precisely when and where BMP4 and nine other hormones were produced in the beaks of fetal finches developing inside their eggs. Of the 10, only BMP4 activity correlated with final beak shape, indicating that the shape depends on when that gene is turned on in beak cells.

In related work, Cheng-Ming Chuong and colleagues at the University of Southern California showed that BMP4 also accounts for the key structural differences between chicken and duck beaks. As final proof of BMP4's key role, they altered those concentrations during development, giving rise to birds with novel beak shapes.

Both reports appeared in the Sept. 3 issue of the journal Science.

-- Rick Weiss

Nine Keys to Heart Attacks

Just nine risky behaviors or medical risk factors account for 90 percent of all heart attacks worldwide, with smoking, high blood-lipid concentrations and stress weighing in as the top three, according to a huge new study.

The individual ranking of those nine varies somewhat depending on where in the world and under what conditions a person lives. But the same nine are the culprits for virtually everyone everywhere, the study found, suggesting that prevention strategies can be applied globally with great benefit.

The 52-country INTERHEART study, led by Salim Yusuf of McMaster University in Canada, included about 15,000 heart attack victims and 15,000 others matched for age, sex and global region. Smoking nearly tripled the risk of a heart attack, and high lipids, such as cholesterol, raised the risk by 3.25. Other top risk factors were stress (2.7), diabetes (2.4), family history of high blood pressure (1.9) and abdominal obesity (1.1).

Three variables proved protective: daily consumption of fruits and vegetables (0.7), regular physical exercise (0.86) and moderate alcohol intake three or fewer times per week (0.91).

The results appear in the Sept. 3 early online version of the Lancet.

-- Rick Weiss