"..Fit People Release More Fat-Burning Molecules During Exercise.."

A new study provides tantalizing clues about how exercise helps ward off heart disease and other ills: Fit people have more fat-burning molecules in their blood than less fit people after exercise.

And the very fittest are even more efficient, on a biochemical level, at generating fat-burning molecules that break down and burn up fats and sugars, the study reports.

A better understanding of these fat-burning molecules, called metabolites, may not only boost athletic performance, but help prevent or treat chronic illnesses such as type 2 diabetes and heart disease by correcting metabolite deficiencies, the researchers said.

The study, apparently the first of its kind, takes a look at how regular exercise -- that is, fitness -- alters metabolism right down to the level of chemical changes in the blood.

"Every metabolic activity in the body results in the product of [fat-burning] metabolites," said senior study author Dr. Robert Gerszten, director of clinical and translational research at Massachusetts General Hospital Heart Center. "A blood sample contains hundreds of these metabolites and can provide a snapshot of any individual's health status."

Previous studies had investigated changes in metabolites generated by exercise, but researchers were limited to viewing a few molecules at a time in hospital laboratories.

But in the new study, a technique developed by the MGH Heart Center in collaboration with MIT and Harvard allowed researchers to see the full spectrum of the fat-burning molecules in action. They used mass spectrometry -- which can analyze blood samples in minute detail -- to develop a "chemical snapshot" of the metabolic effects of exercise.

To trace the fat-burning molecules, the researchers took blood samples from healthy participants before, just following, and after an exercise stress test that was about 10 minutes long. Then they measured the blood levels of 200 different metabolites, which are released into the blood in tiny quantities.

Exercise resulted in changes to levels of more than 20 metabolites that were involved with the metabolism of sugar, fats, amino acids, along with the use of ATP, the primary source of cellular energy, according to the study.

After running on a treadmill for 10 minutes, people who were relatively more fit had a 98% increase in the breakdown of stored fat, sugar, and amino acids, while less-fit people had only a 48% increase.

The very fit had the biggest difference of all. Blood samples taken from 25 people before and after they ran the 2006 Boston Marathon found a 1,128% increase in some key metabolites.

It's unknown whether training boosts the ability of people to burn fat more efficiently, or if more fit people were genetically able to burn fat more efficiently, though it's likely some combination of the two, Gerszten said.

The researchers also found that exercise boosted levels of niacinamide, a vitamin derivative that enhances insulin release.

To investigate what biological mechanisms may be occurring, the researchers applied different combinations of metabolites to muscle cells in a lab. They found that a combination of five molecules shown to be elevated by exercise increased expression of "nur77" -- a gene that research has shown is involved with regulating blood sugar levels and lipid metabolism. The production of the nur77 gene also increased fivefold in the muscles of mice that had exercised for 30 minutes, according to the study.

The gene and its associated metabolites hint at new treatments for metabolic syndrome, a precursor to diabetes, the researchers said.

Abundant research has shown that exercise is beneficial to health, from reducing the risk of heart disease, stroke and type 2 diabetes, to prolonging life, said Emmanuel Skordalakes, an assistant professor in the Gene Expression and Regulation Program at the Wistar Institute in Philadelphia.

Yet researchers are still trying to understand the biological reasons that explain why exercise is good. Studies such as this provide "emerging evidence that begins to explain some of the biological processes and pathways that are regulated during exercise and which have a beneficial effect for us," Skordalakes said.

Even so, far more research has to be done before the research could have a practical application for human performance or illness, Skordalakes said.

"We can't just make these metabolites and gobble them down," Skordalakes said. "It's not as simple as that. These are very complex pathways and that has to be done very carefully."