A new study suggests that one’s exercise tolerance may be nutritionally extended via manipulation of an enzyme linked to muscle fatigue, along with supplementation.
The study appears in the July 7 issue of Cell Metabolism as part of a special issue on “Physical Activity and Metabolic Health,” per a news release from Cell Press.
The researchers first identified an enzyme in skeletal muscle that helps to enhance how much activity a person can tolerate. Muscle cells get their strength from their above-average numbers of mitochondria. Chemical reactions that take place within them use nutrient-derived metabolites to produce energy-rich molecules called ATP and phosphocreatine, which other parts of the cell use to function. An enzyme that generates some of these mitochondrial metabolites, called carnitine acetyltransferase (CrAT), has been known of for many years, but how it contributed to exercise was not known, the release explains.
“To address this gap, we engineered mice that lack the gene-encoding CrAT, specifically in skeletal muscle, and evaluated their ability to perform exercise,” says senior study author Deborah Muoio, a metabolic physiologist at the Duke Molecular Physiology Institute, in the release.
“The CrAT-deficient mice were compared against a control group of genetically identical mice, with the exception of the CrAT gene, which was present and normally active in the controls. We found that the mice lacking CrAT fatigued earlier during various types of exercise tolerance tests because their muscles had more difficulty meeting the energy demands of the activity,” Muoio explains in the release.
Muoio and her team next looked at the relationship between CrAT levels and the ability of human muscles to make energy. To do this, they collaborated with a research team at Maastricht University in the Netherlands who recently developed a noninvasive method for measuring CrAT activity in human muscle. Using this method, they observed that CrAT activity increases with exercise training but decreases in association with aging and age-related metabolic diseases, such as type 2 diabetes, the release explains.
These results led Muoio to question whether the CrAT metabolite could be therapeutically manipulated to possibly enable an individual to exercise longer. One potential candidate to increase CrAT metabolite activity is a micronutrient it uses called carnitine, per the release.
“Although our body makes carnitine, the amount produced declines with age and in certain disease states, implying that supplements might be beneficial in some cases,” Muoio states in the release.
“In further animal studies, we found that carnitine supplementation improved exercise tolerance, but only in the control group with normal CrAT activity in muscle. The results strongly imply that carnitine and the CrAT enzyme work together to optimize muscle energy metabolism during exercise,” Muoio continues in the release.
Muoio and her team found that carnitine supplementation increased exercise stamina in healthy, young adult mice. It is not known, however, whether carnitine can have the same benefits in humans, and the biology behind how CrAT activity improves muscle energy use is still unfolding. Muoio believes that CrAT works to help muscle function by adjusting mitochondrial output when muscles transition from a lower to higher work rate, and vice versa, the release explains.
Her lab is in the process of conducting additional animal studies, as this work has promise to lead to clinical trials in humans, the release states.
“Our priority in the near term is to determine if carnitine supplementation augments the benefits of exercise training in older individuals at risk of metabolic disease,” she says in the release
However, Muoio cautions in the release that the work is not meant to imply that everyone should be taking carnitine supplements.
“We need to move beyond the ‘one size fits all’ approach to optimal nutrition and instead work toward more personalized prescriptions that consider underlying genetics and acquired conditions,” she states in the release.
[Source(s): Cell Press, Science Daily]
