TY - JOUR
T1 - Independent of physical activity, volumetric muscle loss injury in a murine model impairs whole-body metabolism
AU - Dalske, Kyle A.
AU - Raymond-Pope, Christiana J.
AU - McFaline-Figueroa, Jennifer
AU - Basten, Alec M.
AU - Call, Jarrod A.
AU - Greising, Sarah M.
N1 - Publisher Copyright:
© 2021 Public Library of Science. All rights reserved.
PY - 2021/6
Y1 - 2021/6
N2 - Volumetric muscle loss (VML) injuries result in a non-recoverable loss of muscle tissue and function due to trauma or surgery. Reductions in physical activity increase the risk of metabolic comorbidities over time, and it is likely that VML may reduce whole-body activity. However, these aspects remain uncharacterized following injury. Our goal was to characterize the impact of VML on whole-body physical activity and metabolism, and to further investigate possible muscle-specific metabolic changes. Adult male C57Bl/6J (n = 28) mice underwent a standardized VML injury to the posterior compartment of the hind limb, or served as injury naïve controls. Mice underwent longitudinal evaluation of whole-body physical activity and metabolism in specialized cages up to three times over the course of 8 weeks. At terminal time points of 4-and 8-weeks post-VML in vivo muscle function of the posterior compartment was evaluated. Additionally, the gastrocnemius muscle was collected to understand histological and biochemical changes in the muscle remaining after VML. The VML injury did not alter the physical activity of mice. However, there was a noted reduction in wholebody metabolism and diurnal fluctuations between lipid and carbohydrate oxidation were also reduced, largely driven by lower carbohydrate utilization during active hours. Following VML, muscle-specific changes indicate a decreased proportion of fast (i.e., type IIb and IIx) and a greater proportion of slow (i.e., type I and IIa) fibers. However, there were minimal changes in the capillarity and metabolic biochemical activity properties of the gastrocnemius muscle, suggesting a miss-match in capacity to support the physiologic needs of the fibers. These novel findings indicate that following VML, independent of changes in physical activity, there is whole-body diurnal metabolic inflexibility. Supporting future investigations into the chronic and overlooked co-morbidities of VML injury.
AB - Volumetric muscle loss (VML) injuries result in a non-recoverable loss of muscle tissue and function due to trauma or surgery. Reductions in physical activity increase the risk of metabolic comorbidities over time, and it is likely that VML may reduce whole-body activity. However, these aspects remain uncharacterized following injury. Our goal was to characterize the impact of VML on whole-body physical activity and metabolism, and to further investigate possible muscle-specific metabolic changes. Adult male C57Bl/6J (n = 28) mice underwent a standardized VML injury to the posterior compartment of the hind limb, or served as injury naïve controls. Mice underwent longitudinal evaluation of whole-body physical activity and metabolism in specialized cages up to three times over the course of 8 weeks. At terminal time points of 4-and 8-weeks post-VML in vivo muscle function of the posterior compartment was evaluated. Additionally, the gastrocnemius muscle was collected to understand histological and biochemical changes in the muscle remaining after VML. The VML injury did not alter the physical activity of mice. However, there was a noted reduction in wholebody metabolism and diurnal fluctuations between lipid and carbohydrate oxidation were also reduced, largely driven by lower carbohydrate utilization during active hours. Following VML, muscle-specific changes indicate a decreased proportion of fast (i.e., type IIb and IIx) and a greater proportion of slow (i.e., type I and IIa) fibers. However, there were minimal changes in the capillarity and metabolic biochemical activity properties of the gastrocnemius muscle, suggesting a miss-match in capacity to support the physiologic needs of the fibers. These novel findings indicate that following VML, independent of changes in physical activity, there is whole-body diurnal metabolic inflexibility. Supporting future investigations into the chronic and overlooked co-morbidities of VML injury.
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U2 - 10.1371/journal.pone.0253629
DO - 10.1371/journal.pone.0253629
M3 - Article
C2 - 34170933
AN - SCOPUS:85108704151
SN - 1932-6203
VL - 16
JO - PloS one
JF - PloS one
IS - 6 June
M1 - e0253629
ER -