Wednesday, May 25, 2011

Does Fat Actively Restrict Improvement in Muscle Force Generation? The Body Weight-Muscle Mismatch

By GRETCHEN REYNOLDS. Link to original article here:

Recently scientists at Penn State sewed tiny weighted vests and slipped them around the middles of healthy laboratory rats, hoping to discover how animals’ muscles respond to changes in body size. The vests increased the animals’ weight by as much as 36 percent. After five days, the scientists found that the rats’ muscles contained increased amounts of certain proteins involved in the generation of muscle force. The muscles were redesigning themselves to be stronger.

In a separate group of obese rats, however, no such changes were evident. The rats were heavy, generally exceeding the weight of the animals wearing vests, and they continued to pack on ounces during the experiment. But their muscles did not show the same increases in the proteins that improve muscle power. The obese animals were not getting stronger as they became heavier. They were in danger of becoming too fat to move.

How muscles recognize changes in body weight — and why sometimes they don’t — are questions that are likely to have relevance for people, and not just lab rats. Studies have found that “individuals who are extremely overweight often complain that moving is difficult,” said James H. Marden, a professor of biology at Penn State and co-author of the rat study. It’s possible that their muscular strength is not keeping pace with their growing body size.

But why there should be such a mismatch between body weight and muscle strength is unknown. So Dr. Marden and his colleagues began, a few years ago, to study how different creatures deal with changes in their body size and what that might suggest about the human body. They began their work with moths. Flying creatures obviously must deal accurately with body mass or risk plummeting from the sky.

As it turned out, moths are quite good at gauging what they weigh. The bigger the moth, the more its muscles showed activity from one specific gene, the troponin T gene, that expresses various proteins that help muscles to contract. In general, the more of these proteins that a muscle contains, the more forcefully it contracts.
Even when the scientists artificially increased the insects’ body weight, using the simple expedient of gluing lead shot to the moths’ abdomens, the insects’ muscles responded quickly and appropriately. Within days, the troponin T gene in the moths’ wing muscles was pumping out more of the proper proteins to make the muscles stronger. The lead-laden insects had no trouble staying aloft.

But the situation was quite different when the scientists started looking at animals that were fat. Moths don’t become obese, but certain strains of lab rodents do. “We wondered whether there might be a relationship between obesity and the action” of the troponin T gene in muscles, said Rudolf J. Schilder, a postdoctoral fellow at Penn State and lead author of the rat study.

There was. When they biopsied the leg muscles of rats bred to be fat, they found that the chubby animals’ troponin T gene seemed to malfunction. Their muscles contained some of the proteins needed to increase muscle power, but not all of them — and none in as much profusion as in lean rats, even those of a comparable body weight. “The fat rats’ muscles seemed to think that the animals were much smaller than they actually were,” Dr. Schilder said. Their muscles hadn’t come to terms with how fat the animals had become.

Dr. Schilder emphasized that he and his colleagues do not think that troponin T activity, although it is an important marker of muscle function, explains everything about how muscles respond to changes in body weight. The process almost certainly involves a host of other genes and physiological reactions, he said.

It also is not known what mechanisms cause the troponin T gene to malfunction in fat animals, although fat itself is an obvious suspect. “Fat is a very physiologically active tissue,” Dr. Schilder said. “It produces hormones and biochemical messages” that might well disrupt how the troponin T gene functions. Through continuing experiments at his lab, Dr. Schilder hopes to discern more about the role that fat plays in muscle genetics and how much body fat must accumulate before troponin T activity is affected.

But perhaps the most pressing unanswered question about body weight and muscles is what this research means for people. “It’s impossible to know at the moment,” Dr. Marden said, since human studies have not been conducted. But his group’s findings are “suggestive,” he said. “It seems likely” that there are changes in troponin T activity in obese people’s muscles and that, as a result, “it really is physiologically hard for them to move,” he said.

If so, he continued, “we may need to rethink” some exercise programs and suggestions for obese people. “Maybe we should promote activities that require less muscular strain,” he said, like a swim instead of a walk.

“No one is trying to rationalize” remaining heavy, he added, but his group’s work does indicate that misapprehensions about the extent of one’s weight problem may run deep. At the cellular level, muscles and genes may be unable to “understand,” he said, or accept how much a person weighs, a delusion with which many of us, in our minds, can sympathize.