|
Researchers have used NMR to show that endurance-trained athletes have a higher resting muscle metabolism than couch potatoes. The work suggests that the dissociation of oxidation and adenosine triphosphate (ATP) production could be another route by which exercise improves insulin sensitivity and burns excess energy and may have implications for understanding the development of type 2 diabetes. Diabetes is fast becoming a major healthcare issue in the developed world. Importantly, more than nine out of every ten sufferers has the type 2 condition most commonly associated with lack of exercise, poor diet, obesity, and consequently cardiovascular disease. However, while it is well known that insulin resistance plays a primary role in the development of diabetes, the main factors that cause the disease in the first place are unclear. The link with lack of exercise is increasingly apparent, but understanding the role exercise plays in preventing the onset of diabetes remains to be proved. Sports coaches have long suspected that the bodies of finely tuned athletes burn energy faster than sedentary people even without their exercising. But, now Gerald Shulman and colleagues, Douglas Befroy, Kitt Falk Petersen, Sylvie Dufour, Graeme Mason, and Douglas Rothman, in the School of Medicine, at Yale University, in New Haven, Connecticut, have turned to NMR spectroscopy to help them prove the point. "Endurance exercise training is accompanied by physiological changes that improve muscle function and performance," the researchers explain. Fatty acid oxidation has previously been shown to improve in people undergoing endurance training. "Several studies have demonstrated that markers of mitochondrial capacity are elevated, however, these studies tend to be performed ex vivo under conditions that yield maximal enzyme activities or in vivo but monitoring the response to exercise." Because of this problem it is difficult to determine whether exercise influences baseline mitochondrial activity or not. Moreover, conventional calorimetric techniques rather superficially convert whole-body oxygen consumption measurements into muscle metabolism data performed during exercise and so give no insight into baseline mitochondrial function, the team adds. In order to demonstrate whether or not resting muscle metabolism is different between trained and more sedentary people in vivo, the researchers turned to two independent parameters of metabolic function - the tricarboxylic acid (TCA) cycle flux (VTCA) and ATP synthesis (VATP). The researchers have compared the at-rest rate of oxidation and the rate of synthesis of ATP in the calf muscles of seven young endurance runners with eight sedentary volunteers. ATP, more formally, adenosine-5'-triphosphate, is well known as our cells' chemical energy store involved directly in the conversion of food energy into the chemical energy within cells. The team found that although oxidation, the process by which mitochondria consume input material, and more specifically VTCA, was 54 percent higher in the muscle of the athletes, the resting rate of ATP synthesis was similar in all subjects. They also determined the ratio of VATP to VTCA, which they explain is an estimate of mitochondrial coupling and found it to be much lower in the athletes than in the sedentary volunteers. "In this study, we found that resting substrate oxidation, calculated by monitoring the rate of incorporation of [2-13C]acetate into [4-13C]glutamate using 13C NMR, was significantly increased in the muscle of endurance trained male individuals compared with healthy age, height, weight, and sex-matched sedentary subjects," the researchers conclude. The results suggest that the muscles of runners convert more energy to heat even when they are at rest. Technically speaking, the data demonstrate that "basal mitochondrial substrate oxidation is increased in the muscle of endurance trained individuals yet energy production is unaltered, leading to an uncoupling of oxidative phosphorylation at rest," the researchers explain. The researchers point out that exercise training is well known as a means to reverse insulin resistance, a key factor responsible for the onset of type 2 diabetes. Increased exercise seems to boost glucose uptake and fat oxidation and increases the number of mitochondria. In other words, "increased mitochondrial uncoupling may represent another mechanism by which exercise training enhances muscle insulin sensitivity via increased fatty acid oxidation in the resting state." Shulman provided some background on future related work and how it fits with efforts to understand and prevent diabetes. "We are now following up on our other recent PNAS study (Petersen et al 2007) demonstrating a key role for skeletal muscle insulin resistance in promoting atherogenic dyslipidemia associated with the Metabolic Syndrome and working on ways to prevent this," Shulman told SpectroscopyNOW, "We also have an article that will be coming out in Cell next month where we describe a novel gut derived phospholipid that regulates food intake." Reference:
Related links: The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.
|
 Shulman, spectroscopic athlete
|
