Restricted physical activity after volumetric muscle loss alters whole‐body and local muscle metabolism

Raymond‐Pope, Christiana J.; Basten, Alec M.; Bruzina, Angela; McFaline‐Figueroa, Jennifer; Lillquist, Thomas J; Call, Jarrod A.; Greising, Sarah M.

doi:10.1113/jp283959

Cited by 13 publications

(20 citation statements)

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“…VML pathology is also associated with changes in skeletal muscle and whole-body metabolism. For example, following VML injury, there is less mitochondrial respiration in permeabilized myofibers ( Greising et al, 2018 ; Southern et al, 2019 ; McFaline-Figueroa et al, 2022 ), less mitochondrial enzyme activities ( Aurora et al, 2014 ), less activation of PGC1α (genetic marker of mitochondrial biogenesis) ( Aurora et al, 2014 ; Southern et al, 2019 ), and changes in whole-body diurnal metabolism, resulting in lower oxidation of carbohydrates ( Dalske et al, 2021 ; Raymond-Pope et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

The bioenergetic “CK Clamp” technique detects substrate-specific changes in mitochondrial respiration and membrane potential during early VML injury pathology

et al. 2023

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Volumetric muscle loss (VML) injuries are characterized by non-recoverable loss of tissue resulting in contractile and metabolic dysfunction. The characterization of metabolic dysfunction in volumetric muscle loss-injured muscle has been interpreted from permeabilized myofiber respiration experiments involving saturating ADP levels and non-physiologic ATP:ADP concentration ratios. The extent to which this testing condition obscures the analysis of mitochondrial (dys) function after volumetric muscle loss injury is unclear. An alternative approach is described that leverages the enzymatic reaction of creatine kinase and phosphocreatine to assess mitochondrial respiration and membrane potential at clamped physiologic ATP:ADP ratios, “CK Clamp.” The objective of this study was to validate the CK Clamp in volumetric muscle loss-injured muscle and to detect differences that may exist between volumetric muscle loss-injured and uninjured muscles at 1, 3, 5, 7, 10, and 14 days post-injury. Volumetric muscle loss-injured muscle maintains bioenergetic features of the CK Clamp approach, i.e., mitochondrial respiration rate (JO2) titters down and mitochondrial membrane potential is more polarized with increasing ATP:ADP ratios. Pyruvate/malate/succinate-supported JO2 was significantly less in volumetric muscle loss-injured muscle at all timepoints compared to uninjured controls (−26% to −84%, p < 0.001) and electron conductance was less at day 1 (−60%), 5 (−52%), 7 (−35%), 10 (−59%), and 14 (−41%) (p < 0.001). Palmitoyl-carnitine/malate-supported JO2 and electron conductance were less affected following volumetric muscle loss injury. volumetric muscle loss-injury also corresponded with a more polarized mitochondrial membrane potential across the clamped ATP:ADP ratios at day 1 and 10 (pyruvate and palmitoyl-carnitine, respectively) (+5%, p < 0.001). This study supports previous characterizations of metabolic dysfunction and validates the CK Clamp as a tool to investigate bioenergetics in traumatically-injured muscle.

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Section: Introductionmentioning

confidence: 99%

The bioenergetic “CK Clamp” technique detects substrate-specific changes in mitochondrial respiration and membrane potential during early VML injury pathology

et al. 2023

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“…(1.5-2.0%) isoflurane, as previously described (Baltgalvis et al, 2012;McFalin et al, 2022;Raymond-Pope et al, 2023). Briefly, the animal's…”

Section: In Vivo Plantarflexion Muscle Functionmentioning

confidence: 99%

Resistance wheel running improves contractile strength, but not metabolic capacity, in a murine model of volumetric muscle loss injury

Schifino

Raymond‐Pope

Heo

et al. 2023

Experimental Physiology

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The primary objective of this study was to determine if low‐ or high‐resistance voluntary wheel running leads to functional improvements in muscle strength (i.e., isometric and isokinetic torque) and metabolic function (i.e., permeabilized fibre bundle mitochondrial respiration) after a volumetric muscle loss (VML) injury. C57BL/6J mice were randomized into one of four experimental groups at age 12 weeks: uninjured control, VML untreated (VML), low‐resistance wheel running (VML‐LR) and high‐resistance wheel running (VML‐HR). All mice, excluding the uninjured, were subject to a unilateral VML injury to the plantar flexor muscles and wheel running began 3 days post‐VML. At 8 weeks post‐VML, peak isometric torque was greater in uninjured compared to all VML‐injured groups, but both VML‐LR and VML‐HR had greater (∼32%) peak isometric torque compared to VML. All VML‐injured groups had less isokinetic torque compared to uninjured, and there was no statistical difference among VML, VML‐LR and VML‐HR. No differences in cumulative running distance were observed between VML‐LR and VML‐HR groups. Because adaptations in VML‐HR peak isometric torque were attributed to greater gastrocnemius muscle mass, atrophy‐ and hypertrophy‐related protein content and post‐translational modifications were explored via immunoblot; however, results were inconclusive. Permeabilized fibre bundle mitochondrial oxygen consumption was 22% greater in uninjured compared to VML, but there was no statistical difference among VML, VML‐LR and VML‐HR. Furthermore, neither wheel running group demonstrated a change in the relative protein content of the mitochondrial biogenesis transcription factor, peroxisome proliferator‐activated receptor γ coactivator 1‐α (PGC‐1α). These results indicate that resistance wheel running alone only has modest benefits in the VML‐injured muscle.New Findings What is the central question of the study? Does initiation of a resistance wheel running regimen following volumetric muscle loss (VML) improve the functional capacity of skeletal muscle? What is the main finding and its importance? Resistance wheel running led to greater muscle mass and strength in mice with a VML injury but did not result in a full recovery. Neither low‐ nor high‐resistance wheel running was associated with a change in permeabilized muscle fibre respiration despite runners having greater whole‐body treadmill endurance capacity, suggesting resilience to metabolic adaptations in VML‐injured muscle. Resistance wheel running may be a suitable adjuvant rehabilitation strategy, but alone does not fully mitigate VML pathology.

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“…Interestingly, in an elegant experimental approach, published in the Journal of Physiology , Raymond‐Pope et al. (2023) verified the effects of VML on the whole‐body metabolism and muscle function of mice associated with restricted physical activity and/or formoterol treatment (β2‐agonist). Raymond‐Pope and coworkers submitted adult male C57Bl/6J mice to VML surgery, leading to 15% of muscle volume loss.…”

Section: Figure the Main Findings Of The Original Study Of Raymond‐po...mentioning

confidence: 99%

Muscle injury and low physical activity: a potent combination to impair functionality and metabolism

Neto

Ribeiro

Pinto

2023

The Journal of Physiology

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Restricted physical activity after volumetric muscle loss alters whole‐body and local muscle metabolism

Abstract: support-information-section).

Cited by 13 publications

References 50 publications

The bioenergetic “CK Clamp” technique detects substrate-specific changes in mitochondrial respiration and membrane potential during early VML injury pathology

The bioenergetic “CK Clamp” technique detects substrate-specific changes in mitochondrial respiration and membrane potential during early VML injury pathology

Resistance wheel running improves contractile strength, but not metabolic capacity, in a murine model of volumetric muscle loss injury

Muscle injury and low physical activity: a potent combination to impair functionality and metabolism

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