Biology subjects

McGlory, C.

Publications and source records attributed to McGlory, C..

4 recordsLinked to original sources

bioRxiv2026

Dynamic proteomic profiling reveals protein-specific regulation of synthesis rates underpinning the divergent adaptation of human muscle to endurance and resistance training

Endurance (END) or resistance exercise (RE) training results in adaptations that give rise to distinct skeletal muscle phenotypes. Hallmarks of RE include increases in muscle fibre and muscle cross-sectional area and strength, whereas END increases mitochondrial content. Such distinct phenotypes arise from differential metabolic and mechanical signal transduction, transcriptional, and protein translation pathways, culminating in exercise mode-specific adaptations in the muscle proteome. However, little empirical data exist on the protein-specific dynamic responses underlying training-mode-specific adaptations in humans. Using a model of unilateral exercise combined with stable isotope labelling with deuterium oxide, we measured changes in synthesis and abundance from baseline and during early (week 1) and later (week 10) periods of adaptation to END and RE training in young healthy adults (n = 14; 8 female, 6 male; 20 {+/-} 1 y, 70 {+/-} 10 kg). We quantified changes in the abundance (n = 1146 proteins) and synthesis (n = 247 proteins) profiles of skeletal muscle across a 5-day pre-training baseline period and during early and later adaptation to RE and END. Abundance profiling revealed mode-specific proteome remodelling, whereby RE increased ribosomal and contractile protein networks, whereas END increased mitochondrial inner membrane proteins after 10 weeks of training. The protein-specific synthesis rates of 119 proteins showed training-induced differences (P < 0.1 and log2 fold change > 1), including subsets of structural proteins that responded differently to RE and END training modes. Notably, distinct Z-disc proteins, such as XIRP1 (RE-specific) and LDB3 (END-specific), exhibited mode-specific regulation despite sharing a similar subcellular localisation. We report, for the first time, that divergent phenotypic adaptations to RE and END extend beyond changes in bulk fraction-specific synthesis rates and are regulated by training-mode-specific adaptations in distinct protein subsets within similar subcellular protein locations.

physiology↗

bioRxiv2024

Platelet bioenergetics correlate with skeletal muscle metabolism in C57BL/6J mice

Skeletal muscle insulin resistance is a key step in progression of cardiometabolic disease, and impaired mitochondrial bioenergetics has been implicated. However, mitochondrial bioenergetic research in skeletal muscle is limited by the need for muscle biopsies. We sought to determine if platelet bioenergetics could be used as a minimally invasive surrogate for skeletal muscle bioenergetics. Multiple parameters of mitochondrial respiration, measured by high resolution respirometry, correlated between platelets and gastrocnemius muscle in mice. We propose the coupling state of platelet mitochondria reflects that of skeletal muscle in mice, providing a foundation for future research on using platelets as a liquid biopsy for muscle mitochondrial health in cardiometabolic disease, offering early insights into muscle metabolism to enhance clinical biomarker implementation. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=158 SRC="FIGDIR/small/626404v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@1f65c4aorg.highwire.dtl.DTLVardef@125318borg.highwire.dtl.DTLVardef@d7bf1dorg.highwire.dtl.DTLVardef@442926_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2024

Application of 2H2O to quantify red blood cell protein synthesis rates in young trained and untrained males and females

AimCompare the fractional synthetic rate (FSR) of hemoglobin in trained and untrained humans (Hb FSR). MethodsWe employed deuterated water (2H2O) to measure Hb FSR in young males (n=10) and females (n=10) who were aerobically trained (n=5 per sex) and untrained (n=5 per sex). Overall, participants had a mean [Formula] of 49.8 [SD: 10.9] mL/kg/min, hemoglobin mass of 775 [180] g, and red blood cell volume of 2370 [550] mL. After an initial loading dose, participants ingested 2H2O daily for 28 days to maintain a stable 2H body water enrichment ([~]0.9 atom percent deuterium (APD)), as measured in saliva samples collected every 2-3 days. 2H-enriched alanine was measured in RBC protein using gas chromatography combustion isotope ratio mass spectrometry. ResultsThe increase in APD for Hb protein was nonlinear for the first two weeks, but stabilized from day 14 to day 28, with mean APD reaching 0.033 [0.005] % on day 28. Hb FSR calculated over this 2-week period was 0.84 [0.15] %/day, which equated to an Hb absolute synthetic rate of 6.5 [2.2] g/day and a lifespan of 126 [30] days. Hb FSR was not different trained (0.83 [0.19] %/day) and untrained (0.86 [0.24] %/day, P=0.81) individuals or between males (0.80 [0.25] %/day) and females (0.88 [0.17] %/day), P=0.24). ConclusionHabitual endurance training does not appear to affect Hb FSR, but the use of 2H2O to measure Hb FSR in humans has potential applications to many experimental and clinical scenarios.

physiology↗

bioRxiv2024

Network-based modelling reveals cell-type enriched patterns of non-coding RNA regulation during human skeletal muscle remodelling

A majority of human genes produce non-protein-coding RNA (ncRNA), and some have roles in development and disease. Neither ncRNA nor human skeletal muscle is ideally studied using short-read sequencing, so we used a customised RNA pipeline and network modelling to study cell-type specific ncRNA responses during muscle growth at scale. We completed five human resistance-training studies (n=144 subjects), identifying 61% who successfully accrued muscle-mass. We produced 288 transcriptome-wide profiles and found 110 ncRNAs linked to muscle growth in vivo, while a transcriptome-driven network model demonstrated interactions via a number of discrete functional pathways and single-cell types. This analysis included established hypertrophy-related ncRNAs, including CYTOR - which was leukocyte-associated (FDR = 4.9 x10-7). Novel hypertrophy-linked ncRNAs included PPP1CB-DT (myofibril assembly genes, FDR = 8.15 x 10-8), and EEF1A1P24 and TMSB4XP8 (vascular remodelling and angiogenesis genes, FDR = 2.77 x 10-5). We also discovered that hypertrophy lncRNA MYREM shows a specific myonuclear expression pattern in vivo. Our multi-layered analyses established that single-cell-associated ncRNA are identifiable from bulk muscle transcriptomic data and that hypertrophy-linked ncRNA genes mediate their association with muscle growth via multiple cell types and a set of interacting pathways. One Sentence SummaryWe used an optimised transcriptomic strategy to identify a set of ncRNA genes regulated during skeletal muscle hypertrophy in one hundred and forty-four people, with network modelling and spatial imaging providing biological context.

bioinformatics↗