Activation of alternative NF-κB signaling during recovery of disuse-induced loss of muscle oxidative phenotype

Remels, Alexander; Pansters, N.A.M.; Gosker, Harry R.; Schols, A.M.W.J.; Langen, Ramon

doi:10.1152/ajpendo.00452.2013

Cited by 15 publications

(29 citation statements)

References 47 publications

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“…The loss of mitochondrial content and oxidative capacity has been well‐established in different immobilization models in both rat and murine skeletal muscle . More specifically, a decrease in muscle mitochondrial content was reported upon 14 days of UL in the exact same experimental setting as the current murine study, which subsequently recovered during muscle reloading . In line with this, 7 days of strict bedrest, and 14 but not 2 days of human limb immobilization resulted in decreased mitochondrial content markers .…”

Section: Discussionsupporting

confidence: 77%

“…Of interest, mitophagy signaling has not been studied in the early phases of inactivity preceding apparent loss of mitochondrial content. Moreover, many studies have reported expression of mitochondrial dynamics markers in rodent models of muscle inactivity, but convincing evidence indicating increased fission is still lacking . In human studies, it has been shown that expression of key regulators of mitochondrial biogenesis are lower in the skeletal muscle of chronically inactive compared with active subjects, and that transcript abundance of some autophagy‐ and mitophagy‐related markers was lower in inactive subjects .…”

Section: Introductionmentioning

confidence: 99%

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Skeletal muscle unloading results in increased mitophagy and decreased mitochondrial biogenesis regulation

et al. 2019

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IntroductionPhysical inactivity significantly contributes to loss of muscle mass and performance in bed‐bound patients. Loss of skeletal muscle mitochondrial content has been well‐established in muscle unloading models, but the underlying molecular mechanism remains unclear. We hypothesized that apparent unloading‐induced loss of muscle mitochondrial content is preceded by increased mitophagy‐ and decreased mitochondrial biogenesis‐signaling during the early stages of unloading.MethodsWe analyzed a comprehensive set of molecular markers involved in mitochondrial‐autophagy, −biogenesis, −dynamics, and ‐content, in the gastrocnemius muscle of C57BL/6J mice subjected to 0‐ and 3‐days hind limb suspension, and in biopsies from human vastus lateralis muscle obtained before and after 7 days of one‐leg immobilization.ResultsIn both mice and men, short‐term skeletal muscle unloading results in molecular marker patterns indicative of increased receptor‐mediated mitophagy and decreased mitochondrial biogenesis regulation, before apparent loss of mitochondrial content.DiscussionThese results emphasize the early‐onset of skeletal muscle disuse‐induced mitochondrial remodeling.

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Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Skeletal muscle unloading results in increased mitophagy and decreased mitochondrial biogenesis regulation

et al. 2019

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“…Indeed, as expected upon exercise training, C1 displayed an increase in OXCAP markers upon PR, reflecting a restoration of the oxidative metabolic machinery. This is corroborated by the decreased expression of oxidative metabolism regulation markers, as a normalization of metabolism‐related mRNA has previously been shown in late‐stage muscle regeneration . Conversely, in C2, oxidative metabolism regulation and OXCAP were statistically unaltered, although oxidative metabolism regulation seemed to increase upon PR.…”

Section: Discussionsupporting

confidence: 77%

Distinct skeletal muscle molecular responses to pulmonary rehabilitation in chronic obstructive pulmonary disease: a cluster analysis

Kneppers

Haast

Langen

et al. 2019

J cachexia sarcopenia muscle

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Background Pulmonary rehabilitation (PR) is a cornerstone in the management of chronic obstructive pulmonary disease (COPD), targeting skeletal muscle to improve functional performance. However, there is substantial inter‐individual variability in the effect of PR on functional performance, which cannot be fully accounted for by generic phenotypic factors. We performed an unbiased integrative analysis of the skeletal muscle molecular responses to PR in COPD patients and comprehensively characterized their baseline pulmonary and physical function, body composition, blood profile, comorbidities, and medication use. Methods Musculus vastus lateralis biopsies were obtained from 51 COPD patients (age 64 ± 1 years, sex 73% men, FEV 1 , 34 (26–41) %pred.) before and after 4 weeks high‐intensity supervised in‐patient PR. Muscle molecular markers were grouped by network‐constrained clustering, and their relative changes in expression values—assessed by qPCR and western blot—were reduced to process scores by principal component analysis. Patients were subsequently clustered based on these process scores. Pre‐PR and post‐PR functional performance was assessed by incremental cycle ergometry and 6 min walking test (6MWT). Results Eight molecular processes were discerned by network‐constrained hierarchical clustering of the skeletal muscle molecular rehabilitation responses. Based on the resulting process scores, four clusters of patients were identified by hierarchical cluster analysis. Two major patient clusters differed in PR‐induced autophagy ( P < 0.001), myogenesis ( P = 0.014), glucocorticoid signalling ( P < 0.001), and oxidative metabolism regulation ( P < 0.001), with Cluster 1 (C1; n = 29) overall displaying a more pronounced change in marker expression than Cluster 2 (C2; n = 16). General baseline characteristics did not differ between clusters. Following PR, both 6 min walking distance (+26.5 ± 8.3 m, P = 0.003) and peak load on the cycle ergometer test (+9.7 ± 1.9 W, P < 0.001) were improved. However, the functional improvement was more pronounced in C1, as a higher percentage of patients exceeded the minimal clinically important difference in peak workload (61 vs. 21%, P = 0.022) and both peak workload and 6 min walking test (52 vs. 8%, P = 0.008) upon PR. Conclusions We identified patient groups with distinct skeletal muscle molecular responses to rehabilitation, associated with differences in functional improvements upon PR.

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“…Conversely, decreased physical activity results in altered signaling pathways leading to loss of skeletal muscle mass and decreased muscle oxidative metabolism [241–244] . PGC-1α is highly responsive to muscle contraction and has been extensively examined for the regulation of oxidative metabolism by physical activity [87,245] .…”

Section: Cancer Cachexia-induced Regulation Of Skeletal Muscle Oximentioning

confidence: 99%

The emerging role of skeletal muscle oxidative metabolism as a biological target and cellular regulator of cancer-induced muscle wasting

Carson

Hardee

VanderVeen

2016

Seminars in Cell & Developmental Biology

131

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While skeletal muscle mass is an established primary outcome related to understanding cancer cachexia mechanisms, considerable gaps exist in our understanding of muscle biochemical and functional properties that have recognized roles in systemic health. Skeletal muscle quality is a classification beyond mass, and is aligned with muscle's metabolic capacity and substrate utilization flexibility. This supplies an additional role for the mitochondria in cancer-induced muscle wasting. While the historical assessment of mitochondria content and function during cancer-induced muscle loss was closely aligned with energy flux and wasting susceptibility, this understanding has expanded to link mitochondria dysfunction to cellular processes regulating myofiber wasting. The primary objective of this article is to highlight muscle mitochondria and oxidative metabolism as a biological target of cancer cachexia and also as a cellular regulator of cancer-induced muscle wasting. Initially, we examine the role of muscle metabolic phenotype and mitochondria content in cancer-induced wasting susceptibility. We then assess the evidence for cancer-induced regulation of skeletal muscle mitochondrial biogenesis, dynamics, mitophagy, and oxidative stress. In addition, we discuss environments associated with cancer cachexia that can impact the regulation of skeletal muscle oxidative metabolism. The article also examines the role of cytokine-mediated regulation of mitochondria function regulation, followed by the potential role of cancer-induced hypogonadism. Lastly, a role for decreased muscle use in cancer-induced mitochondrial dysfunction is reviewed.

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Activation of alternative NF-κB signaling during recovery of disuse-induced loss of muscle oxidative phenotype

Abstract: Remels AH, Pansters NA, Gosker HR, Schols AM, Langen RC. Activation of alternative NF-B signaling during recovery of disuseinduced loss of muscle oxidative phenotype.

Cited by 15 publications

References 47 publications

Skeletal muscle unloading results in increased mitophagy and decreased mitochondrial biogenesis regulation

Skeletal muscle unloading results in increased mitophagy and decreased mitochondrial biogenesis regulation

Distinct skeletal muscle molecular responses to pulmonary rehabilitation in chronic obstructive pulmonary disease: a cluster analysis

The emerging role of skeletal muscle oxidative metabolism as a biological target and cellular regulator of cancer-induced muscle wasting

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