Metabolic Impairment Occurs Without Changes in Physical Activity in Volumetric Muscle Loss

Abstract

As the primary organ of movement, skeletal muscle requires flexible fuel selection to support varying levels of physical activity. For instance, at low levels of activity and during rest, lipids are the primary source of fuel, while carbohydrates are utilized for higher levels of activity. Physical activity is essential for optimal skeletal muscle health and function, and lack of physical activity is associated with various metabolic impairments, such as metabolic inflexibility, a state where skeletal muscle loses efficiency when transitioning between fuel sources. Over time, metabolic inflexibility increases the risk of developing various metabolic comorbidities, such as obesity, diabetes, and heart disease, among others. Metabolic inflexibility can be ameliorated with physical activity and increasing physical activity, however various conditions may impair skeletal muscle and increase the likelihood of inactivity. Orthopaedic injury is an example of a condition that has been shown to reduce physical activity, both acutely and chronically, increasing the risk of metabolic inflexibility and metabolic disorder. Volumetric muscle loss (VML) injury, in which muscle is abruptly lost through traumatic or surgical events, is one such orthopaedic trauma. It is likely that reductions in physical activity and whole-body metabolic impairments occur following VML, however, physical activity and whole-body metabolic outcomes are currently not characterized in the literature. To address this lack of knowledge, a study was designed to evaluate physical activity and whole-body metabolic function at 4 and 8 weeks post-VML injury. The principal finding was that metabolic inflexibility developed independently of changes in physical activity levels following VML injury and that underlying pathophysiologic changes to the muscle may contribute to maladaptive changes at the whole-body level. These findings support that VML injury may increase the risk of metabolic comorbidities, and that future efforts may need to mitigate metabolic maladaptation alongside regenerative and rehabilitative endeavors.