Writing in the journal Cell Metabolism, focused on a metabolic enzyme called carnitine acetyltransferase (CrAT), which uses the micronutrient carnitine to boost the energy economy within mitochondria.
The US-based researchers noted that while CrAT has been known for many years, its role in exercise was unknown: “Acylcarnitine metabolites have gained attention as biomarkers of nutrient stress, but their physiological relevance and metabolic purpose remain poorly understood,” wrote the authors – led by senior author Dr Deborah Muoio at Duke University.
"Exercise intolerance becomes a problem when reduced strength and stamina prevent normal, routine activities such as mowing the lawn or climbing stairs, or when physical activity causes extreme discomfort," said Muoio. "So finding ways to optimize exercise could have tremendous impact to improve overall health."
"We were actually quite surprised that carnitine supplementation proved beneficial in young, healthy mice because our presumption was that carnitine availability was not a limiting factor under these circumstances," she added.
"We don't know yet if these results will hold true in humans.”
Muoio and her colleagues examined the impact of skeletal-muscle-specific CrAT deficiency on muscle bioenergetics, acetyl group balance, and exercise stamina in mice.
The team engineered mice that lack the gene encoding CrAT, specifically in skeletal muscle, and evaluated their ability to perform exercise. These CrAT-deficient mice were compared against a control group of mice that were identical, except they had the CrAT gene.
As suspected, 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 researchers then introduced a carnitine supplement – which was found improve exercise tolerance only in animals with normal CrAT activity in muscle.
Muoio said these results strongly imply that carnitine and the CrAT enzyme work together to optimize muscle energy metabolism during exercise.
“Our findings not only establish important roles for CrAT and acetylcarnitine in modulating muscle energy economy during contraction but also suggest that nutritional and/or pharmacological strategies aimed at promoting CrAT activity could prove useful for offsetting metabolic inertia, delaying muscle fatigue, and combatting exercise intolerance,” wrote the team.
Clinical trials and additional animal studies are underway to define the role of CrAT in muscle energy metabolism.
Muoio added 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.
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.
"This work is not meant to imply that everyone should be taking carnitine supplements," said Muoio. "We need to consider underlying genetics, lifestyle factors and acquired conditions."
Source: Cell Metabolism
Volume 22, Issue 1, Pages 65–76, 7 July 2015, doi: 10.1016/j.cmet.2015.06.003
"Carnitine Acetyltransferase Mitigates Metabolic Inertia and Muscle Fatigue during Exercise"
Authors: Sarah E. Seiler, Timothy R. Koves, et al