Lower Plasma Lactate Concentrations After Training Support the Hypothesis of Improved Metabolic Flexibility in Male Long-Term Selected Marathon Mice Compared to Unselected Controls DOI Creative Commons
Julia Brenmoehl,

Zianka Meyer,

Christina Walz

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(24), P. 2123 - 2123

Published: Dec. 21, 2024

Metabolic flexibility describes the capability to switch between oxidative fuels depending on their availability during diet or exercise. In a previous study, we demonstrated that in response training, marathon (DUhTP) mice, paternally selected for high treadmill performance, are metabolically more flexible than unselected control (DUC) mice. Since exercise-associated metabolic can be assessed by indirect calorimetry partially circulating lactate concentrations, investigated these parameters DUhTP and DUC Therefore, males of both lines completed three-week high-speed training were physically inactive (sedentary) before being placed cage three days (one day acclimatization, two with monitoring), measuring CO2 O2 calculate respiratory quotient (RQ) fatty acid oxidation (FATox). Circulating blood concentrations determined. Training resulted lower RQ an increased mice compared sedentary counterparts. Increased FATox rates observed exercised but not indicating shift metabolism glycolytic one improved is verifiable up after training.

Language: Английский

Exercise-Specific Adaptations in Human Skeletal Muscle: Molecular Mechanisms of Making Muscles Fit and Mighty DOI Creative Commons

Aaron C. Q. Thomas,

Connor A. Stead, Jatin G. Burniston

et al.

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 223, P. 341 - 356

Published: Aug. 13, 2024

The mechanisms leading to a predominantly hypertrophied phenotype versus oxidative phenotype, the hallmarks of resistance training (RT) or aerobic (AT), respectively, are being unraveled. In humans, exposure naïve persons either AT RT results in their skeletal muscle exhibiting generic 'exercise stress-related' signaling, transcription, and translation responses. However, with increasing engagement RT, responses become refined, typically associated each form exercise emerges. Here, we review some underpinning adaptations how muscles become, through AT, 'fit' 'mighty.' Much our understanding molecular physiology has arisen from targeted analysis post-translational modifications measures protein synthesis. Phosphorylation specific residue sites been dominant focus, canonical signaling pathways (AMPK mTOR) studied extensively context respectively. These alone, along synthesis, have only begun elucidate key differences signaling. Still, yet uncharacterized exist regulation synthesis that drive unique adaptation RT. Omic studies required better understand divergent relationship between phenotypic outcomes training.

Language: Английский

Citations

8
Molecular aspects of the exercise response and training adaptation in skeletal muscle DOI Creative Commons
Regula Furrer, Christoph Handschin

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 223, P. 53 - 68

Published: July 24, 2024

Skeletal muscle plasticity enables an enormous potential to adapt various internal and external stimuli perturbations. Most notably, changes in contractile activity evoke a massive remodeling of biochemical, metabolic force-generating properties. In recent years, large number signals, sensors, regulators effectors have been implicated these adaptive processes. Nevertheless, our understanding the molecular underpinnings training adaptation remains rudimentary. Specifically, mechanisms that underlie signal integration, output coordination, functional redundancy other complex traits are unknown. fact, it is even unclear how stimulus-dependent specification brought about endurance or resistance exercise. this review, we will provide overview on events describe acute perturbations single exercise bouts. Furthermore, insights into principles long-term adaptation. Finally, current gaps knowledge be identified, strategies for multi-omic –cellular analyses skeletal engaged individual, bouts chronic discussed.

Language: Английский

Citations

7
Methylome–proteome integration after late‐life voluntary exercise training reveals regulation and target information for improved skeletal muscle health DOI Creative Commons
Toby L. Chambers, Andrea Dimet‐Wiley, Alexander R. Keeble

et al.

The Journal of Physiology, Journal Year: 2024, Volume and Issue: 603(1), P. 211 - 237

Published: July 26, 2024

Exercise is a potent stimulus for combatting skeletal muscle ageing. To study the effects of exercise on in preclinical setting, we developed combined endurance-resistance training mice called progressive weighted wheel running (PoWeR). PoWeR improves molecular, biochemical, cellular and functional characteristics promotes aspects partial epigenetic reprogramming when performed late life (22-24 months age). In this investigation, leveraged pan-mammalian DNA methylome arrays tandem mass-spectrometry proteomics to provide detailed information late-life adaptations female relative age-matched sedentary controls (n = 7-10 per group). Differential CpG methylation at conserved promoter sites was related transcriptional regulation genes as well Nr4a3, Hes1 Hox after PoWeR. Using holistic method -omics integration binding expression target analysis (BETA), changes were associated with upregulated proteins global mitochondrial translation (P 0.03). Specifically, BETA implicated control ribosomal, mitoribosomal, complex I protein abundance training. may also influence LACTB, MIB1 UBR4 induction - all are mechanistically linked health. Computational cistrome predicted several transcription factors including MYC regulators trained methylome-proteome landscape, corroborating prior transcriptome data. Correlating proteome mass fatigue resistance revealed positive relationships VPS13A NPL levels, respectively. Our findings expose differential proteomic translational that could function aged mice. KEY POINTS: Late-life from 22-24 age shown improve vivo promote mitigation. Integration 36k using (which contain ageing clock sites) exploratory extends our work reveals coordinated widespread initiation, ribosomal (mitoribosomal) voluntary sizeable cohort group analysis). Multi-omics serine β-lactamase-like (LACTB tumour muscle), mind bomb 1 (MIB1 satellite cell type 2 fibre maintenance) ubiquitin ligase E3 component N-recognin 4 (UBR4 quality control) identified regulator proteome, agreement analyses. Vacuolar sorting 13 homolog A (VPS13A) positively correlated mass, glycoprotein/glycolipid sialylation enzyme N-acetylneuraminate pyruvate lyase (NPL) resistance.

Language: Английский

Citations

6
Resistance exercise‐induced circulating factors influence the damaged skeletal muscle proteome in a sex‐dependent manner DOI Creative Commons
Hui‐Ying Luk, Danielle E. Levitt,

Casey R. Appell

et al.

Physiological Reports, Journal Year: 2025, Volume and Issue: 13(7)

Published: April 1, 2025

Abstract Muscle recovery after damage is mediated by circulating factors and intracellular signaling pathways. Our previous studies have demonstrated that resistance exercise (RE)‐induced elicited sex‐differential responses in damaged muscle. However, the global effects of these on muscle are largely understudied. We examined differential RE‐induced sex proteome. Damaged vastus lateralis from 3 men women a parent study were analyzed. Participants completed 2 identical bouts unilateral eccentric knee extensions immediately followed either upper body RE to induce (EXE) or 20‐min seated rest (CON). biopsies collected leg at 24 h used. 900 proteins identified LC–MS/MS analysis. Ingenuity Pathway Analysis was used detect activation prediction using z‐scores for functional pathway analyses. In men, 79 downregulated 15 upregulated EXE versus CON. These differentially expressed associated with immunological inflammatory Biological functions vs. CON include inactivating acute signaling, neutrophil extracellular trap ROS production, activating IL‐12 signaling. results underline sex‐specific effect proteome, where immune altered but not women. Given response critical damage, highlight potential role could be essential mediating recovery.

Language: Английский

Citations

0
CD47-blocking antibody confers metabolic benefits against obesity DOI Creative Commons

Y. J. Su,

Jingyu Sun, Xiaobo Li

et al.

Cell Reports Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 102089 - 102089

Published: April 1, 2025

CD47-blocking antibody is a well-known potential drug for tumor immunotherapy. However, it unclear whether can protect against metabolic disorders. We report that high-fat diet (HFD)-induced obesity increases CD47 expression, while exercise downregulates in skeletal muscle. Administration of mice prevents HFD-induced weight gain and glucose intolerance, enhances capacity, improves body composition muscle mitochondrial function. Mechanistically, the protective effects conferred by are mediated through activation AMP-activated protein kinase (AMPK) Consistently, muscle-specific CD47-knockout show similar improvements, indicating direct role regulating AMPK vivo. Furthermore, reduces phosphorylation heat shock 90α (HSP90α) to activate In conclusion, confers benefits activating pathway

Language: Английский

Citations

0
Sex differences in skeletal muscle metabolism in exercise and type 2 diabetes mellitus DOI
Kirstin A. MacGregor, Stian Ellefsen, Nicolas J. Pillon

et al.

Nature Reviews Endocrinology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 27, 2024

Language: Английский

Citations

0
Sexual dimorphism in molecular profiles of resting human skeletal muscle and the response to acute exercise and endurance training DOI Creative Commons
Simon I. Dreher, Thomas Goj, Christine von Toerne

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 13, 2024

Abstract Biological sex has a strong impact on skeletal muscle metabolism and performance. By comprehensive investigation of epigenetic, transcriptomic proteomic differences between female male untrained subjects we provide molecular basis for the sexual dimorphism glucose lipid metabolism. The sex-specific multi-OMICs profiles indicate higher degree turnover abundance fast-twitch fibers in males high handling females. Eight-week endurance training equalized initial toward an endurance-trained profile both sexes. females was more resistant to acute exercise challenge since stress-responsive transcripts were predominantly upregulated males. In myotubes from same donors, hardly conserved, but could be partially restored by treatment with hormones. conclusion, after only 8 weeks mitigates deeply rooted common metabolically beneficial response.

Language: Английский

Citations

0
Lower Plasma Lactate Concentrations After Training Support the Hypothesis of Improved Metabolic Flexibility in Male Long-Term Selected Marathon Mice Compared to Unselected Controls DOI Creative Commons
Julia Brenmoehl,

Zianka Meyer,

Christina Walz

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(24), P. 2123 - 2123

Published: Dec. 21, 2024

Metabolic flexibility describes the capability to switch between oxidative fuels depending on their availability during diet or exercise. In a previous study, we demonstrated that in response training, marathon (DUhTP) mice, paternally selected for high treadmill performance, are metabolically more flexible than unselected control (DUC) mice. Since exercise-associated metabolic can be assessed by indirect calorimetry partially circulating lactate concentrations, investigated these parameters DUhTP and DUC Therefore, males of both lines completed three-week high-speed training were physically inactive (sedentary) before being placed cage three days (one day acclimatization, two with monitoring), measuring CO2 O2 calculate respiratory quotient (RQ) fatty acid oxidation (FATox). Circulating blood concentrations determined. Training resulted lower RQ an increased mice compared sedentary counterparts. Increased FATox rates observed exercised but not indicating shift metabolism glycolytic one improved is verifiable up after training.

Language: Английский

Citations

0