Research from Everest: Can leucine help burn fat and spare muscle tissue during exercise?

Research on Mt. Everest climbers is adding to the evidence that an amino acid called leucine — found in foods, dietary supplements, energy bars and other products — may help people burn fat during periods of food restriction, such as climbing at high altitude, while keeping their muscle tissue. It was one of two studies reported here today at the 242nd National Meeting & Exposition of the American Chemical Society (ACS) on the elite corps of men and women who have tackled the highest peak on Earth, mountaineering’s greatest challenge.

In a pilot study of the feasibility of supplementing the diet of climbers with the branch chain amino acid, leucine, scientists studied 10 climbers for 6-8 weeks as they ascended Mt. Everest, which towers 29,000 feet above sea level. Since Sir Edmund Hillary and Sherpa guide Tenzing Norgay made the first successful climb in 1953, over 2,500 people have scaled Mt. Everest in the Himalayas. Thousands more tried and failed, with more than 216 deaths. The researchers were studying the physiological benefits of adding leucine to the climbers’ diets to help them stay healthy. The researchers are from the University of Utah.

Wayne Askew, Ph.D., and his co-investigator, Stacie Wing-Gaia, Ph.D., who headed the leucine study, explained that the extreme weather conditions, low oxygen levels, treacherous terrain and strenuous exercise during such climbs create a huge nutritional challenge. Weight loss at high altitude is exactly the opposite problem that is on the minds of millions of people in the United States and other countries who are trying to shed excess weight. Climbers often cannot or do not eat enough calories, failing to replenish their bodies with important nutrients. They lose both fat and muscle during an arduous climb, endangering their strength and motor coordination. At high altitudes, fat and muscle loss occurs not only when they are climbing, but also at rest.

“The significant part about this weight loss is that a disproportionate amount comes from the muscle mass,” said Askew. “This can be a problem on long expeditions at high altitude because the longer climbers are there and the higher they go, the weaker they get. The body breaks down the muscle for energy, so climbers don’t have it available for moving up the mountain.

“We knew that leucine has been shown to help people on very low-calorie, or so-called ‘calorie-restricted diets’, stay healthy at sea level,” said Askew. “It’s one of the components, the building blocks, of protein. But no one had tested whether leucine would help people stay healthy and strong at high altitudes, so we added leucine to specially prepared food bars that we gave to the climbers.”

Askew didn’t climb Mt. Everest, but members of his research team, Dr. Wing-Gaia and Dr. Rodway, went to base camp and measured expedition members’ fat and muscle by using an ultrasound device placed on the skin. They are currently examining the data to see whether climbers who ate the leucine bar retained more muscle than those who ate a bar without leucine. One finding that was apparent early on in the study was that the food item in which the leucine was delivered was critically important. The Everest climbers had difficulties consuming the three food bars per day that contained the additional leucine. Askew stressed that this was a small pilot study to test the feasibility of leucine supplementation at altitude, so definitive conclusions of its benefits at altitude await the results of a more controlled clinical study. The researchers plan to improve the palatability of the leucine food vehicle in consultation with military food product developers at Natick Research Development and Engineering Center and conduct a more controlled study at high altitude, possibly with the U.S. Army Institute of Environmental Medicine at their laboratory on Pike’s Peak.

Askew pointed out that the findings also could help people at lower altitudes who want to lose weight while preserving their lean body mass, or who are elderly and don’t eat or exercise enough to maintain their strength. He predicts that consumers might one day see leucine-rich bars on grocery store shelves, especially at high-altitude locations, such as Aspen and Denver, where high-altitude skiing and climbing activities are popular.

In the other Everest report, John Finley, Ph.D., described a study in which he gave Mt. Everest climbers a type of fat called “medium-chain triglycerides” in their cookies and hot chocolate. They also took an aspirin every day.

“We tried to improve climbers’ performances by feeding them medium-chain triglycerides — fat that we thought would be metabolized better as quick energy,” said Finley, who is with Louisiana State University.

At high altitudes, the air pressure is low and the oxygen is less dense — making less oxygen available for breathing. In response, the body makes more oxygen-carrying red blood cells. This thickens the blood and puts a strain on the heart and lungs, increasing the risk of potentially dangerous blood clots. That’s why Finley also had the climbers take aspirin, which is known for thinning the blood and reducing the risks of having a heart attack or stroke. “We found that we could reduce the risk factors involved in having more viscous blood at high altitudes by giving the climbers aspirin,” he said.

Finley himself went on the climb and collected urine and fecal samples. The climbers who consumed the medium-chain triglycerides lost less weight and performed better than others on the expedition. The data also suggested that fats aren’t absorbed well at high altitudes when the body is losing a lot of weight, possibly because too little bile is produced by the liver to dissolve the fats, he explained.

Finley doesn’t have plans to commercialize the medium-chain triglyceride hot chocolate and cookies, but suggests that people going to high-altitude locations talk with their health-care providers about taking a daily aspirin.

Provided by American Chemical Society (news : web)

Molecular muscle: Small parts of a big protein play key roles in building tissues

 

We all know the adage: A little bit of a good thing can go a long way. Now researchers in London are reporting that might also be true for a large protein associated with wound healing.

The team at the Kennedy Institute of Rheumatology at Imperial College reports in the Journal of Biological Chemistry that a protein generated when the body is under stress, such as in cases of physical trauma or disease, can affect how the protective housing that surrounds each cell develops. What's more, they say, tiny pieces of that protein may one day prove useful in preventing the spread of tumors or fibrosis.

At just 174 nanometers in diameter, tenascin-C is pretty big in the world of proteins, and it looks a lot like a spider with six legs, which are about 10 times longer than its body. Thanks to those long legs, tenascin-C can do real heavy lifting when it comes to wound healing.

"Tenascin-C plays many roles in the response to tissue injury, including, first of all, initiating an immune response and, later, ensuring proper tissue rebuilding," explains Kim Midwood, who oversaw the project.

When the injury alarm is rung, tenascin-C shows up on the scene and attaches to another protein, fibronectin. Together, tenascin-C and fibronectin help to construct the housing, or extracellular matrix, that surrounds each cell.

"The extracellular matrix is the home in which the cells of your body reside: It provides shelter and nutrients and also sends signals to the cell to tell it how to behave," says Midwood. "To make a finished tissue, the matrix must be carefully built."

Tenascin-C's job is a temporary one. When your hand is cut, for example, it appears at the edges of the wound and then goes away when scar tissue develops, says postdoctoral research associate Wing To: "Tenascin-C is thought to play a major role during the rebuilding phase of tissue injury by promoting regeneration of tissue that has been damaged."

If the extracellular matrix were a construction site, tenascin-C could be seen as the scaffold upon which the weaving of fibronectin threads, or fibrils, is done. "Tenascin-C has multiple arms, and we have shown that it has multiple binding sites for fibronectin," Midwood says. "In this way, it can bind to many fibronectin fibrils at once and help to form the whole tissue by linking the fibrils together. Then, when the repair is done, the scaffolding is taken down."

Midwood and To systematically determined where tenascin-C and fibronectin bind together. They also identified small parts of tenascin-C, known as domains, that can bind to only one fibronectin fibril apiece.

"The small domains act as caps of the scaffold. No more fibronectin fibrils can bind once these caps are in place," Midwood says. So, in essence, they found that certain pieces of tenascin-C determine when fibril building should stop once enough, but not too much, tissue is made.

The findings could be especially useful for creating therapies for conditions in which there is aberrant extracellular matrix deposition, such as in cancers, fibrotic conditions or chronic non-healing wounds, adds To.

In abnormal conditions, such as in the case of a tumor cell, "the home that's made of fibronectin helps it to survive, shelters it and provides signals that enable it to proliferate," says Midwood. "As the tumor thrives, the home keeps on growing, expanding to destroy the existing neighborhood."

Similarly, in fibrotic diseases, tissue rebuilding rages out of control – with too much fibronectin assembly – so that it takes over the whole affected organ, Midwood says.

"In the end, we found that tenascin-C has both stop and go functions cleverly concealed in the same molecule," Midwood says. "The large spiderlike protein may provide a scaffold for building, and the small domains of the protein block excess building. Small domains may be therapeutically useful in situations where too much fibronectin drives disease."

If certain domains can stop uncontrolled matrix deposition in conditions where there is an increase in unwanted extracellular matrix, such as in fibrosis, then they could be useful tools for controlling such diseases.

Meanwhile, To says, in conditions with high levels of tenascin-C degradation by enzymes, for example in nonhealing chronic wounds, that may expose active tenascin-C domains, "if we can stop the production of these domains during disease progression with specific inhibitors, maybe we could help ameliorate the condition.

Similarly we could try and get the cells to make tenascin-C variants that are not as easily broken down by enzymes to help facilitate wound healing."

More information: Midwood and To's paper was named a "Paper of the Week" by the Journal of Biological Chemistry.

Provided by American Society for Biochemistry and Molecular Biology