Using a system that analyzes blood samples with unprecedented detail, a team led by Massachusetts General Hospital (MGH) researchers has developed the first "chemical snapshot" of the metabolic effects of exercise. Their findings, reported in the May 26 issue of Science Translational Medicine, may improve understanding of the physiologic effects of exercise and lead to new treatments for cardiovascular disease and diabetes.

"We found new metabolic signatures that clearly distinguish more-fit from less-fit individuals during exercise," says Gregory Lewis, MD, of the MGH Heart Center, the paper's lead author. "These results have implications for the development of optimal training programs and improved assessment of cardiovascular fitness, as well as for the development of nutritional supplements to enhance exercise performance."

The beneficial health effects of exercise -- including reducing the risk of heart disease, stroke and type 2 diabetes -- are well known, but the biological mechanisms underlying those effects are unclear. Previous investigations of exercise-induced changes in metabolites -- biological molecules produced in often-minute quantities -- have focused on the few molecules measured by most hospital laboratories.

Using a new mass-spectrometry-based system that profiles more than 200 metabolites at a time -- developed in collaboration with colleagues from the Broad Institute of Harvard and MIT, led by Clary Clish, PhD -- the MGH-based team analyzed blood samples taken from healthy participants before, immediately following, and one hour after exercise stress tests that were approximately 10 minutes long.

Exercise-associated changes were seen in more than 20 metabolites, reflecting processing of sugars, fats and amino acids as fuels as well as the body's utilization of ATP, the primary source of cellular energy. Several changes involved metabolic pathways not previously associated with exercise, including increases in niacinamide, a vitamin derivative known to enhance insulin release.

Another experiment that analyzed samples taken from different vascular locations indicated that most metabolite changes were generated in the exercising muscles, although some appeared to arise throughout the body. In both experiments, several metabolite changes persisted 60 minutes after exercise had ceased.

In an experiment designed to assess the effects of prolonged exercise, pre- and post-race samples were taken from 25 runners who completed the 2006 Boston Marathon. Extensive changes in several metabolites -- some different from those produced by brief exercise -- were seen in the post-race samples. Indicators of increased metabolism of fats, glucose and other carbohydrates rose in response to both brief and prolonged exercise, but in marathoners amino acid levels also fell significantly, reflecting their use of amino acids as fuel to maintain adequate glucose levels during extended exercise.

The researchers also analyzed how these metabolite changes related to participants' level of fitness -- determined by peak oxygen uptake in the short-term experiments and by finishing times for the marathon runners. In both groups they found that several changes, including those reflecting increased fat metabolism, were more pronounced in participants who were more fit.

Pursuing the hypothesis that metabolites which increase in response to exercise act on pathways involved in cellular respiration and glucose utilization, the investigators applied different combinations of metabolites to cultured muscle cells. They found that a combination of five molecules increased expression of nur77, a gene recently shown to regulate glucose levels and lipid metabolism, making it a possible treatment target for the combination of cardiovascular risk factors known as metabolic syndrome. The association of nur77 levels with exercise was supported by an experiment that found gene expression increased fivefold in the muscles of mice that had exercised for 30 minutes.

"Our results have implications for development of both diagnostic testing to track and improve exercise performance and for interventions to reduce the effects of diabetes or heart disease by improving a patient's metabolic 'fingerprint'," explains Robert Gerszten, MD, director of Clinical and Translational Research at the MGH Heart Center, the study's senior author. "Improving the health of people with cardiovascular disease is our number one goal, but defining which metabolites become deficient and need to be replenished during exercise could also lead to the next generation of sports drinks that can help healthy individuals achieve their best exercise performance."

Source: Massachusetts General Hospital

See also: High Intensity Workout Gets The Job Done and Exercise Burns Fat During But Not After Your Workout

Cross-country skiing is one of the most demanding of all Olympic sports, with skiers propelling themselves at speeds that exceed 20-25 km per hour over distances as long as 50 km. Yet the difference between winners and losers in these grueling races can be decided by just the tip of a ski, as a glance at any recent world-class competition will show. So just what gives top racers the advantage?

In an article to be published in the European Journal of Applied Physiology, Øyvind Sandbakk, a PhD candidate in the Norwegian University of Science and Technology's Human Movement Science Programme, reports with his colleagues on the metabolic rates and efficiencies of world-class skiers. Sandbakk's research offers a unique window on what separates the best from the rest in the world of elite cross-country racers.

"Skiers need high aerobic and anaerobic energy delivery, muscular strength, efficient techniques and the ability to resist fatigue to reach and maintain top speeds races," Sandbakk says. Those physical attributes may not be so very different from other world-class athletes, except that cross-country skiers also need to have mastered a variety of techniques and tempos, depending upon the course terrain, Sandbakk notes.

These challenges mean that the importance of the athlete's different physical capacities will differ in different sections of races, and between different types of competitions. For example, during the 10- and 15-km freestyle (skate) races in the Vancouver Olympics (the first of which are scheduled for February 15, with a 10km women's race and a 15 km men's race), skiers with high aerobic power (often referred to as maximal oxygen uptake per kilo body mass) will have an advantage in maintaining high speeds during the race, especially in the uphill terrain, Sandbakk says.

He says it is the uphill terrain that normally separates skiers the most during freestyle races. However, the 10- and 15-km courses also contain a great deal of level terrain, where an athlete with higher muscle mass and anaerobic power may have the edge needed to win.

Cross-country skiing also challenges skiers to master a great range of techniques for different speeds and slopes. Sandbakk predicts this factor will be crucial in the technically difficult Vancouver competition tracks. In skating races, skiers have as many as seven different skiing techniques (much like the gears on a bicycle) at their disposal, and they constantly shift between these different techniques during a single race.

"Skiers even adapt these seven techniques depending on the speed and slope," Sandbakk says. "The best skiers tend to ski with longer cycle lengths (the number of metres a skier moves his centre of mass per cycle), but with a similar cycle frequency," he says. "But during the last part of the race, the cycle frequency seems to be higher in the better skiers."

Another crucial aspect of technique is when the skier pushes off with his or her skate ski, and the skier's ability to recover quickly from the tremendous physical demand of providing a forceful push. "The ability to resist fatigue seems tightly coupled to the ability to maintain technique and keep up the cycle lengths and frequencies during a race," Sandbakk says. "In two skiers of otherwise equal fitness, this may be the deciding factor during the last part of the race in determining who wins the gold."

See also: The Physiology Of Speed and For Rock Climbers, Endurance Is Key To Performance

Source: The Norwegian University of Science and Technology (NTNU) and Metabolic rate and gross efficiency at high work rates in world class and national level sprint skiers. European Journal of Applied Physiology