The benefits of exercise are well known, but physical fitness becomes increasingly difficult as people age or develop ailments, creating a downward spiral into poor health. Now, researchers at Duke Medicine report there may be a way to improve exercise tolerance and, by extension, its positive effects. The new study describes a small molecule and its metabolic pathway that work together to optimize energy use in exercising muscles. In mouse studies, animals that received a nutrient supplement that increased activity of this pathway ran longer and farther than those that were not supplemented. The opensource study is published in the journal Cell Metabolism.
The current study focused on a metabolic enzyme called carnitine acetyltransferase, or CrAT, which uses the micronutrient carnitine to boost the energy economy within mitochondria, the tiny engines of cells. The team note that CrAT has been known about for many years, however, its role in exercise was unidentified. To investigate this the researchers engineered mice that lack the gene encoding CrAT, specifically in skeletal muscle, and evaluated their ability to perform exercise. The CrAT-deficient mice were compared against a control group of mice that were identical, except they had the CrAT gene.
As suspected, the data findings showed mice that lacked the CrAT gene tired earlier during various exercise tests because their muscles had more difficulty meeting the energy demands of the activity. The lab then introduced a carnitine supplement. The results showed that exercise tolerance improved only in animals with normal CrAT activity in muscle. The team state that these results strongly imply that carnitine and the CrAT enzyme work together to optimize muscle energy metabolism during exercise.
The researchers note that the findings suggest that CrAT and the metabolite it produces help the mitochondrial engines respond more efficiently when muscles transition from a low to higher work rate, and vice versa. They go on to stress that more research is needed to fully understand how this system improves energy economy during exercise, as well as validate the findings in human studies.
The team state that responses to any given exercise regimen or intervention can vary tremendously among individuals, which means that both genetic and environmental factors influence exercise-induced improvements in physical fitness and overall health. Nutrition is one of those factors, and the lab say they are interested in identifying nutritional strategies to augment the positive effects of physical activity. The current study suggests that the CrAT enzyme might be targetable through such strategies.
For the future the researchers state that clinical trials and additional animal studies are underway to define the role of CrAT in muscle energy metabolism. The lab go on to add that the short-term goal is to determine whether carnitine supplementation enhances the benefits of exercise training in older individuals at risk of metabolic disease. their long-term plans include efforts to identify other genes and metabolic pathways that influence individual responses to exercise intervention, with the goal of developing personalized programs to optimize the health benefits gained by physical activity.
The team conclude that this work is not meant to imply that everyone should be taking carnitine supplements as human trials have not been completed and futures studies need to consider underlying genetics, lifestyle factors and acquired conditions.
Source: Duke Medicine